key: cord-338855-1hfj8qj9 authors: dr adylle varon, l.; varon, daryelle s.; varon, joseph title: traditional chinese medicine and covid-19: should emergency practitioners use it? date: 2020-07-03 journal: am j emerg med doi: 10.1016/j.ajem.2020.06.076 sha: doc_id: 338855 cord_uid: 1hfj8qj9 nan j o u r n a l p r e -p r o o f released an integrated treatment program to be implemented. classical herbal formulas, such as yu ping feng san, sang ju yin and yin qiao san, were highly sought out for prevention and treatment of in this issue of the american journal of emergency medicine, sun and coworkers present an adept metanalysis supporting the clinical efficacy and safety of using tcm herbal prescriptions for the treatment of covid-19. 7 the article incorporates, in detail, the results from seven studies, with 681 participants utilizing tcm as a therapeutic course of treatment. the results are interesting and encouraging. however, we suggest that we recognize that these outcomes may have some intrinsic issues. for example, we are concerned that the depicted results reflect a steady state of illness, whereas in tcm, measures can vary depending on which herbal formulations are administered, and the stage or rate of infection in each patient. tcm methodology used to diagnose and treat any pathology heavily relies on the time of exposure for all ailments. other limitations of this metanalysis include the many variables of patient demographics, different herbal preparations, and access to funding to purchase such preparations. the authors are transparent and need to be applauded for their data analysis. indeed, they suggest the results gathered could be, in fact, fallible. clinical features of patients infected with 2019 novel coronavirus in first case of 2019 novel coronavirus in the united states 2020 epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area traditional chinese medicine treatment of covid-19 combination of western medicine and chinese traditional patent medicine in treating a family case of covid-19 the role of chinese medicine in covid-19 pneumonia: a systematic review and meta-analysis key: cord-333872-shhugvx0 authors: kumar, jitendra; khatana, p.s.; raina, rajni title: the conundrum of rising covid19 infection among health care workers: an emerging paradigm date: 2020-07-04 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.001 sha: doc_id: 333872 cord_uid: shhugvx0 nan in your esteemed journal has drawn our attention and we read it very keenly. many other reports along with our own experience which we are sharing here, strongly suggests that we need to think outside the box to protect our hcws in the current challenging situation. first of all, we would like to illustrate few of the case events which we witnessed in our own tertiary care hospital. one unsuspected case of a young male with acute abdomen was being conservatively managed for a week then suddenly he developed respiratory distress. his in the beginning of the pandemic, lack of knowledge about covid19 was blamed for infection among hcws [4, 5] . maybe it is true but with time, situation is not improving either. in fact, in some cases it has become worse [6, 7] . so far, most of the reports cited reason for this large number of infections among hcws are lack of resources like ppe kits, lack of infection control training, long working hours & stressful environment and particular procedure with potential of high aerosol generation [4] [5] [6] . not only an article by smereka j. et al. [2] but almost every relevant article on the safety issues of hcws has paid lot of attention to personal protection kit (ppe) for protection of hcws while available evidence is not strong enough that makes it 100% effective [8] . with the time, issue of asymptomatic hcws infected with covid19 has also become a big concern. such asymptomatic infected hcws can transmit infection unknowingly to the patients and other hcws. at one of the london hospital, sample for rt-pcr testing for covid19 taken from asymptomatic and healthy hcws at multiple point of time. in a total number of 1,479 health care worker's sample, 1.1% to 7.1% (at different point of time) were found positive for covid19 [9] . that's why, now epidemic surveillance and routine testing at multiple point of time for every hcws including asymptomatic one is strongly recommended [10] . worse of all, no country around the world is tracking or reporting any data related to covid19 infection among hcws. w.h.o. and international council of nurses (icn) raised serious concern regarding lack of data of covid19 related infection and deaths among hcws. in spite of this, no steps have so far been taken by any concerned authorities across the world. unless we maintain transparency in record keeping related to covid19 infection among hcws, we can't analyse and prevent it further. covid-19 in health care workers -a systematic review and meta-analysis the use of personal protective equipment in the covid-19 pandemic era covid-19 and the risk to health care workers: a case report death from covid-19 of 23 health care workers in china covid-2019) infection among health care workers and implications for prevention measures in a tertiary hospital in wuhan, china healthcare workers & sars-cov-2 infection in india: a case-control investigation in the time of covid-19 covid-19 and italy: what next? personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff covid-19: pcr screening of asymptomatic health-care workers at london hospital covid-19: the case for health-care worker screening to prevent hospital transmission key: cord-027892-5ik9f6nx authors: so, mitsuhito; hifumi, toru; isokawa, shutaro; shimizu, masato; otani, norio; ishimatsu, shinichi title: the authors' response: a diagnostic confusion between serotonin syndrome and neuroleptic malignant syndrome date: 2020-06-25 journal: am j emerg med doi: 10.1016/j.ajem.2020.06.048 sha: doc_id: 27892 cord_uid: 5ik9f6nx nan the authors' response: a diagnostic confusion between serotonin syndrome and neuroleptic malignant syndrome dear editor: thank you for the comments on our article. first, we could not describe the details of symptoms or the differential diagnosis in the text because of the word limit; therefore, we sincerely appreciate the authors/editors providing us the opportunity to describe the details of neuroleptic malignant syndrome (nms) in patients with covid-19 infection. the authors proposed a possible diagnosis of serotonin syndrome (ss) in our reported two cases of nms following covid-19 infection because both cases fulfilled the sternbach's criteria of ss [1] . however, several aspects must be addressed to differentiate nms from ss in these cases. first, although ss is characterized by neuromuscular hyperreactivity (tremor, hyperreflexia, and myoclonus), these physical findings were not detected in the two cases. second, remarkably elevated creatine kinase levels were observed. third, the authors described that rapid onset and rapid resolution of fever pattern were more likely in ss, rather than in nms; however, the high-grade fever (>39°c) persisted for approximately five days in case 1 and three days in case 2. fourth, another case of nms in a patient with covid-19 infection has been recently published [2] . in case 1, hyperreactivity symptoms such as tremor and myoclonus were not observed. furthermore, although there was no rigidity of the major joints, rigidity of the fingers on both sides was recognized. in addition, there was no history of use of selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. this patient had loose stools and watery stools since the time of admission, but no apparent improvement was observed even after the discontinuation of the causative drugs. in case 2, hyperreactivity and rigidity findings such as tremor and myoclonus were not recognized. although not pursued in the submitted paper, we started suvorexant (orexin receptor antagonist) on day 5 at the same time as risperidone for treating delirium. later, risperidone was discontinued on day 8 owing to the suspicion of nms, but suvorexant was not considered to be the causative drug and continued without discontinuation until day 20. despite continuing suvorexant, as there was improvement in the symptoms, this drug cannot be considered as a causative agent. this patient had loose stools and mud stools since the time of admission, but no improvement was found even after the discontinuation of suvorexant. although no typical symptoms of ss were observed, a possibility of coexistence of both nms and ss exists, as the authors proposed. therefore, as we have proposed in the manuscript, careful consideration of the development of nms is necessary in the management of patients with covid-19 infection [3] . the serotonin syndrome neuroleptic malignant syndrome in a covid-19 patient neuroleptic malignant syndrome in patients with covid-19 key: cord-263753-p3evgngz authors: magoon, rohan title: dexmedetomidine in covid-19: probing promises with prudence! date: 2020-10-27 journal: am j emerg med doi: 10.1016/j.ajem.2020.10.034 sha: doc_id: 263753 cord_uid: p3evgngz nan dilatation, interstitial extravasations and vascular stasis that can have a deleterious impact on the subsequent morbidity and mortality in this vulnerable subset [4] . in addition, common risk-factors such as obesity for dex-associated hyperthermia and covid-related mortality, compound the situation furthermore [4] . long-term infusions of dexmedetomidine dex raises a concern for the withdrawal phenomenon. this can be all the more troublesome in covid-19 cohort with descriptions accumulating on the prolonged sedation requirement in this setting [5, 6] . while the peak dex-doses >0.8 µg/kg/hr and daily cumulative dex-doses >12.9 µg/kg/day have been described to be associated with an elevated withdrawal incidence [7] , lack of presentation of the contextual dexdose administered in the covid-19 patient featured in the stockton and kyle-sidell case-report, captivates attention [1] . however, withdrawal can be prevented with the meticulous use of drug or mitigated with clonidine [5] . (iii) in addition, once on invasive mechanical ventilation, a precision approach to sedation in covid-19 patients, as epitomized by payen et al, appears to be prudent centralising the focus on inter-individual variability and synchronizing the level of ventilator support to the subsequent target of sedation, thereby directing the subsequent choice of sedative agents, including dex [8, 9] . the discussion highlights that proposition of novel therapies should be associated with a beckon to err on the side of caution so as to assist physicians make informed decisions and exercise appropriate vigil, very much the case in the aforementioned context as we still ardently await the results of ongoing studies such as: 'use of dexmedetomidine in light to infection' (prodex, nct04350086) and 'immunomodulatory profile of dexmedetomidine dexmedetomidine and worsening hypoxemia in the setting of covid-19: a case report potential therapeutic value of dexmedetomidine in covid-19 patients admitted to icu dexmedetomidine-associated hyperthermia: a series of 9 cases and a review of the literature dexmedetomidine-associated hyperpyrexia in three critically ill patients with coronavirus disease sedation, analgesia, and paralysis in covid-19 patients in the setting of drug shortages covid-19: icu delirium management during sars-cov-2 pandemic incidence of dexmedetomidine withdrawal in adult critically ill patients: a pilot study sedation for critically ill patients with covid-19: which specificities? one size does not fit all implications of practice variability: comment pulmonary vasculature in covid-19: mechanism to monitoring compounded research challenges amid the covid-19 pandemic we do not have any conflict of interest, any commercial or financial interest in this material & agree to abide by the rules of your journal regarding publication of this article.author roles: rm conceptualized and wrote the entire comment. key: cord-338922-wew3hety authors: miller, kelsey a.; mannix, rebekah; schmitz, gillian; monuteaux, michael c.; lee, lois title: impact of covid-19 on professional and personal responsibilities of massachusetts physicians date: 2020-08-27 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.051 sha: doc_id: 338922 cord_uid: wew3hety • the professional impact is more uniform but the personal impact varies by specialty & demographics. • physicians report minimal change in employment status but half report a decrease in income. • emergency medicine physicians have experienced quarantining from family at a higher frequency. • female physicians report spending more hours on child and household care and less time on selfcare. state and city-level stay-at-home orders/advisories during the covid-19 pandemic are an essential part of the public health response. these advisories directly and indirectly impact the professional and personal lives of physicians. 1 before the pandemic, gender differences in work-life balance were present, 2,3 and pandemic related impacts will potentially exacerbate these inequities. physician organizations have focused on physician wellness in the face of this pandemic. to target interventions, it is important to understand the pandemic-related impacts on physician work and life. 4 this study examines changes in the professional status and personal responsibilities of physicians related to the covid-19 pandemic and the stay-at-home advisories. this is a cross-sectional, observational study of massachusetts emergency medicine (em) and pediatric physicians. they were selected to characterize effects of a single state's stay-at-home advisory among physicians with different clinical impacts from covid-19. this study was deemed exempt by the institutional review board. massachusetts re-opening. the primary outcomes were changes in work hours and income and changes in hours spent on home-related care. we calculated descriptive statistics and comparative analyses between demographic and specialty groups using the chi square or fisher's exact test (tests two-tailed, alpha at 0.05). analyses were performed using stata statistical software v. 16.0 (statacorp, college station, tx). the survey was returned by 205/1640 mcaap (13%) and 76/792 macep members (10%), for 281 respondents total (table 1 ). questions about professional and personal responsibilities were completed by 260. most respondents reported no change in employment (96%), but 47% reported a current or anticipated decrease in income. pediatric physicians (8%) were more likely to experience a change in their employment status compared to em and pediatric em (pem) physicians (0%, p < 0.05). a minority (5%) of respondents reported being furloughed. there were no statistically significant differences by gender in changes to employment status or income. overall, 14% of physicians quarantined from their families. em/pem physicians (20%) were more likely to have quarantined than pediatric physicians (8%, p < 0.05). most physicians reported spending increased time on childcare, home schooling and household care (figure 1 ). this was accompanied by a decrease in hours spent on their professional physician duties and on self-care. more men (28.9%) reported increased hours spent on professional responsibilities compared to women (15.9%, p=0.02). females spent more hours on childcare and household care than males we report an early perspective of the personal and professional impacts of the covid-19 pandemic on em and pediatric physicians. overall there was minimal change in employment; however, half experienced income decreases. this has been reported at a practice level, but the individual level impacts are less well described. 5 there were greater personal domain effects with one in five em/pem physicians quarantined from their family. our study has limitations, including the potential for responder and recall bias, generalizability with surveying em and pediatric physicians in one state, and the limited response rate. our study supports concerns for increased professional gender disparities during the pandemic stayat-home advisory, 2 including fewer scientific publication submissions by women compared to men. 6 these may be due in part to the hypothesized differential effects of school closures on women. 7 in our study, female physicians invested more time in child and household care and less time on selfcare and professional responsibilities, compared to men. awareness of gender-specific impacts is important or we risk continuing to exacerbate gender disparities in wage and leadership. understanding these effects is also important to inform targeted efforts to support physician wellness and mitigate the long-term impacts of the covid-19 pandemic on physicians. supporting the health care workforce during the covid-19 global epidemic doctoring while woman women physicians and the covid-19 pandemic areas of academic research with the impact of covid-19 immediate and long-term impact of the covid-19 pandemic on delivery of surgical services the decline of women's research production during the coronavirus pandemic | nature index covid-19: the gendered impacts of the outbreak key: cord-316513-dbzj101e authors: sen-crowe, brendon; mckenney, mark; elkbuli, adel title: utilizing technology as a method of contact tracing and surveillance to minimize the risk of contracting covid-19 infection date: 2020-07-04 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.003 sha: doc_id: 316513 cord_uid: dbzj101e nan j o u r n a l p r e -p r o o f currently, there are two major forms of testing in the u.s.: testing for sars-cov-2 rna and serologic testing. 1, 2 however, only testing those experiencing symptoms is not a practical way of obtaining a true picture of the infection status of the nation, as the majority of infected individuals do not exhibit symptoms. 3 healthcare personnel who are in close contact with ill patients may be asymptomatic themselves and unknowingly transmit the infection to others. a call for new methods of testing and surveillance on a large scale will be important if we hope to control the spread of sars-cov-2 infections. fortunately, advancements in technology allow diagnostics and surveillance to be readily available. one innovative approach that has gained popularity is the use of a smart ring. on example is the oura ring (ooura health ltd.'s, oulu, finland) which can detect physiologic changes and alert the possibility of infection. understanding changes in vital signs such as body temperature, respiratory and heart rate may enable early detection of signs of infection. for example, one study at west virginia univeristy, rockefeller neuroscience institute predicted symptoms 24 hours prior to onset based on physiologic changes detected by the oura ring, and aim to achieve a 3-day forecast in the future. 4 implementation of preventative measures before symptoms are apparent when there may be a risk of viral shedding may translate into a much larger benefit than we anticipate and has the potential to reduce infection in other healthcare workers and patients. in addition, early detection and contact tracing has the potential to conserve hospital resources that have become scarce throughout the pandemic. for example, there has been a shortage of ventilators. 5 areas that have been flagged as high-risk due to surveillance can be supplied with additional hospital resources to match their case load. hence, targeted distribution of hospital resources to these areas can make the difference for a hospital to adequately treat those in critical condition without the need for triaging treatment between patients. testing for covid-19 cdc diagnostic test for covid-19 transcript for the cdc telebriefing update on covid-19 wvu rockefeller neuroscience institute and oura health unveil study to predict the outbreak of covid-19 in healthcare professionals ventilator stockpiling and availability in the us. johns hopkins center for health security australian government -department of health key: cord-341060-otvoo99j authors: alharthy, abdulrahman; faqihi, fahad; papanikolaou, john; balhamar, abdullah; blaivas, mike; memish, ziad a.; karakitsos, dimitrios title: thrombolysis in severe covid-19 pneumonia with massive pulmonary embolism date: 2020-07-30 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.068 sha: doc_id: 341060 cord_uid: otvoo99j objective: no guidelines exist for the management of massive pulmonary embolism (pe) in covid-19. we present a covid-19 patient with refractory acute respiratory syndrome (ards), and life-threatening pe who underwent successful thrombolysis. case presentation: a previously healthy 47 year old male was admitted to our hospital due to severe covid-19 pneumonia [confirmed by real-time-polymerase-chain-reaction (rt-pcr)]. he had rapidly evolving ards [partial arterial pressure of oxygen to fractional inspired concentration of oxygen ratio: 175], and sepsis. laboratory results showed lymphocytopenia, and increased d-dimer levels (7.7 μg/ml; normal: 0–0.5 μg/ml). the patient was treated in the intensive care unit. on day-1, ards-net/prone positioning ventilation, and empiric anti-covid treatment integrating prophylactic anticoagulation was administered. on hospital day-2, the patient developed shock with worsening oxygenation. point-of-care-ultrasound depicted a large thrombus migrating from the right atrium to the pulmonary circulation. intravenous alteplase (100 mg over 2 h) was administered as rescue therapy. the patient made an uneventful recovery, and was discharged to home isolation (day-20) on oral rivaroxaban. conclusion: thrombolysis may have a critical therapeutic role for massive pe in covid-19; however the risk of potential bleeding should not be underestimated. point-of-care ultrasound has a pivotal role in the management of refractory ards in covid-19. j o u r n a l p r e -p r o o f evolving ards [partial arterial pressure of oxygen to fractional inspired concentration of oxygen ratio: 175], and sepsis. laboratory results showed lymphocytopenia, and increased ddimer levels (7.7 mcg/ml; normal: 0-0.5 mcg/ml). the patient was treated in the intensive care unit. on day-1, ards-net/prone positioning ventilation, and empiric anti-covid treatment integrating prophylactic anticoagulation was administered. on hospital day-2, the patient developed shock with worsening oxygenation. point-of-care-ultrasound depicted a large thrombus migrating from the right atrium to the pulmonary circulation. intravenous alteplase (100 mg over two hours) was administered as rescue therapy. the patient made an uneventful recovery, and was discharged to home isolation (day-20) on oral rivaroxaban. thrombolysis may have a critical therapeutic role for massive pe in covid-19; however the risk of potential bleeding should not be underestimated. point-of-care ultrasound has a pivotal role in the management of refractory ards in covid-19. keywords: covid-19, massive pulmonary embolism, thrombolysis, acute respiratory distress syndrome, point-of-care ultrasound. recently, a preliminary analysis of a large us cohort of critically ill patients with severe novel sars-cov-2 disease (covid-19) has suggested the benefit of systemic anticoagulation on their j o u r n a l p r e -p r o o f anticoagulation in patients with severe covid-19, and padua prediction score ≥4 or d-dimer>3.0 μg/ml has been previously suggested due to the increased occurrence of pulmonary embolism (pe) [3, 4] . scarce data exist though about the use and safety of thrombolysis for massive pe in patients with covid-19. herein, we are briefly discussing the case of a critically ill covid-19 patient who underwent thrombolysis for life-threatening pe. a previously healthy 47 year old male was admitted to our emergency department due to severe suppl. video 1. point-of-care-cardiac ultrasound modified four-chamber view (day-2) revealing a large thrombus in a dysfunctional right heart "en-route" to the pulmonary circulation in our critically ill covid-19 patient. suppl. video 2. point-of-care-cardiac ultrasound modified four-chamber view (day-5) depicting no thrombi in the right heart, and normalization of right ventricular function in our critically ill covid-19 patient. anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy incidence of thrombotic complications in critically ill icu patients with covid-19 comparative performance of sars-cov-2 detection assays using seven different primer/probe sets and one assay kit detection of sars-cov-2 in different types of clinical specimens coagulopathy and antiphospholipid antibodies in patients with covid-19 saudi ministry of health. coronavirus diseases 19 (covid-19) guidelines. (revised version thromboprophylaxis with rivaroxaban in acutely ill medical patients with renal impairment: insights from the magellan and mariner trials severe pulmonary embolism in covid-19 patients: a call for increased awareness deep vein thrombosis in hospitalized patients with coronavirus disease 2019 (covid-19) in wuhan, china: prevalence, risk factors, and outcome china medical treatment expert group for covid-19 clinical characteristics of coronavirus disease 2019 in china. china medical treatment expert group for covid-19 clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study covid-19 lombardy icu network. baseline characteristics and outcomes of 1591 patients infected with sars-cov admitted to icus of the lombardy region, italy cardiac involvement in a patient with coronavirus disease 2019 (covid-19) first case of covid-19 complicated with fulminant myocarditis: a case report and insights covid-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options covid-19 and the heart cardiovascular considerations for patients, health care workers, and health systems during the covid-19 pandemic endothelial cell infection and endotheliitis in covid-19 catheter-directed thrombolysis in covid-19 pneumonia with acute pe: thinking beyond the guidelines a prospective, longitudinal evaluation of point-ofcare lung ultrasound in critically ill patients with severe covid-19 pneumonia key: cord-253657-fminkpas authors: maslanka, maciej; smereka, jacek; czyzewski, lukasz; ladny, jerzy robert; dabrowski, marek; szarpak, lukasz title: vie scope® laryngoscope versus macintosh laryngoscope with personal protective equipment during intubation of covid-19 resuscitation patient date: 2020-09-04 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.085 sha: doc_id: 253657 cord_uid: fminkpas nan dear editor, airway management is a key element of resuscitation procedures. however, due to the current covid-19 pandemic, medical personnel should complete medical procedures wearing full personal protective equipment (ppe) for aerosol-generating procedures (agp) [1] . ppe-agp should be used especially during cardiopulmonary resuscitation, including airway management [2] . emergency intubation using direct laryngoscopy carries a significant risk of failure. as many authors indicate, the effectiveness of the first intubation attempt with a macintosh laryngoscope is from 57.6% to 89.9% [3, 4] . the use of ppe-agp may reduce the efficiency of medical procedures and prolong their duration [5, 6] . intubation methods alternative to macintosh laryngoscope may be a suitable solution. an example of a new type of laryngoscope is vie scope® (androit surgical, oklahoma city, usa), which is a self-contained, battery-powered, disposable scope that takes advantage of a closed circular tube with a beveled end to visualize the vocal cords (figure 1) . the light is transmitted through the sidewall of the tube from end to end as well as within the lumen of the tube. the intubation procedure using vie scope® should be based on the following steps -the intubator should: (1) insert scope and identify glottis opening between vocal cords, (2) pass the bougie under direct vision between the vocal cords into the trachea, (3) remove the scope leave the bougie in place, (4) pass the endotracheal tube over the bougie into the trachea, (5) remove the bougie, (6) ventilate. the aim of this study was to evaluate intubation performance by paramedics wearing ppe-agp using macintosh laryngoscope and vie scope® laryngoscope under simulated resuscitation of covid-19 patient. the study was designed as a prospective randomized crossover simulation trial. the study protocol was approved by the institutional review board of the polish society of disaster medicine (no. 15.11.2019.irb). 42 working paramedics took part in the study. voluntary informed consent was obtained from each participant. none of the participants had previous experience with the vie scope® laryngoscope. before the examination, the participants took part in the presentation of the laryngoscope and the method of correct intubation using it. the study participants then attended a 20-minute practical training course during which they performed endotracheal intubation using vie scope® under normal airway conditions. during the target study, paramedics dressed in full ppe-agp were to perform endotracheal intubation with continuous chest compression. endotracheal intubation was performed using macintosh laryngoscope (mac; blade no.3) as well as with vie scope® laryngoscope (vsc). the advanced simman 3g adult patient simulator (stavanger, norway) was used to simulate a patient requiring endotracheal intubation. a standard intubation guide was used for mac and a bougie guide for vsc. each participant had a maximum of 3 attempts to intubate using each device. both the order of participants and intubation methods were random. a detailed randomization procedure is presented in supplementary figure 1 . the data were blinded for the team interpreting the results. the results were analyzed using the statistical package statistica 13.3en (tibco inc., usa) or review manager 5.4en (cochrane collaboration, oxford, uk). group differences in dichotomous data are expressed as odds ratios (ors) and group differences in continuous data as mean differences (mds), both with 95% confidence intervals (cis). the fixed-effect model was used to pool the results. duration of intubation when one attempt needed between distinct intubation methods varied and amounted to 44 (iqr; 40.5-53)sec. for mac and 28. 5 1.93; p=0.13 ). the ease of intubation is based on the vas scale (0 -"easy procedure" to "10" -difficult procedure) varied and amouted to 5 (iqr, 4-8) vs. 2 (iqr; 2-5) points (md=2.75; 95%ci: 2.34, 3.16; p<0.001). in conclusion, under the conditions of intubation performed by paramedics wearing ppe-agp with continuous chest compression, the results of the study indicate higher efficiency of intubation with vie scope® compared to macintosh laryngoscope in terms of both the efficiency of the first intubation attempt and the time of the procedure. further studies are required to confirm the results. figure 1 respiratory protection among healthcare workers during cardiopulmonary resuscitation in covid-19 patients covid-19 in healthcare workers the utility of the c-mac as a direct laryngoscope for intubation in the emergency department comparison of the time to successful endotracheal intubation using the macintosh laryngoscope or kingvision video laryngoscope in the emergency department: a prospective observational study resuscitation of the patient with suspected/confirmed covid-19 when wearing personal protective equipment: a randomized multicenter crossover simulation trial video laryngoscopy for endotracheal intubation of adult patients with suspected/ confirmed covid-19. a systematic review and metaanalysis of randomized controlled trials key: cord-334705-vclkuink authors: sokas, claire m.; berrigan, margaret t.; fligor, scott c.; fleishman, aaron j.; raven, kristin e.; rodrigue, james r. title: is social distancing keeping patients from the ed?() date: 2020-07-16 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.025 sha: doc_id: 334705 cord_uid: vclkuink nan in response to covid-19, public health organizations issued recommendations to limit transmission. these recommendations include physical distancing, frequent hand hygiene, and use of personal protective equipment (ppe). 1,2 in conjunction with state-level mandated shelter-in-place orders and the closure of schools and non-essential businesses, daily life in the u.s. has changed dramatically. we sought to characterize perceptions of public health recommendations and explore the decision to seek medical care for common symptoms. we conducted a 39-question survey assessing attitudes and behaviors associated with public health recommendations. to understand the impact on individual medical decision making, we asked participants to describe their approach to care for common symptoms before and during the pandemic, classifying behaviors according to escalation of care: 1) stay home and see if it gets better ("wait and see"); 2) call my doctor; 3) present to an emergency department (ed), urgent care (uc), or call 911. we recruited u.s. adults fluent in english in mid-april 2020. the survey was administered via amazon mechanical turk. 3 descriptive statistics were calculated. multivariable logistic regression was used to investigate for predictors of escalation or de-escalation of care. data were analyzed using stata version 16. 937 respondents were included. mean age was 37.9 and most were white (74%), male (59%), medically insured (83%), college educated (50%), and without chronic health conditions (73%). all states were represented and most participants (84%) lived in area state with a stay-at-home order in place. the majority of patients followed centers for disease control recommendations for daily behaviors "often" or "all the time" (figure 1 ). most participants followed recommendations to work from home (74%), go out only for essential errands (77%) wash hands frequently (87%) and practice social distancing (89%); only half wore a mask in public. more than half of participants were "very" or "extremely" concerned about their personal and family's health. about half (54.1%) felt that is they contracted covid-19, they would develop a severe illness and 10% believed they would be unable to recover. most participants agreed or strongly agreed the novel coronavirus affected their daily work, family, or social activities (91%), that it is important for the general public to follow recommendations of public health officials (93%), and the pandemic will be shorter if public health recommendations are followed (88%). medical decision making before and after the start of the covid-19 pandemic is visualized in figure 2 . for all symptoms, there was an increase in "call your doctor" during the pandemic. however, fewer patients would present to an ed or uc for respiratory symptoms during the pandemic (chest pain: 38  33%), while rates of evaluation for abdominal pain and arm/leg weakness remained consistent. multivariable logistic regression of predictors of de-escalation of care did not identify any predictors consistent across all four symptoms. males were more likely to de-escalate care for shortness of breath or weakness of an arm/leg (odds ratio ( at the onset of the covid-19 pandemic in april 2020, u.s. adults adapted their behaviors in accordance with public health recommendations and believed these mandates would lessen the impact of the pandemic. participants reported changing how they would seek care for common symptoms, with an increase in "call my doctor" for all symptoms and a decrease in seeking emergency care for respiratory symptoms-despite covid-19 causing primarily respiratory symptoms. this highlights the increasing role of telemedicine during this crisis and the need to further investigate how patients seek medical care. reduced ed visits and hospital admissions for common diagnoses during the pandemic have been puzzling-our findings highlight the importance of understanding and addressing health-related worries to understand changes in behaviors. 4, 5 fear and uncertainty are common. most participants worry about their own and their family's health, their ability to obtain medical care, and prolonged, severe illness if they contracted covid-19. when people are concerned about their health, they are more likely to alter their behavior. 6 although our survey cohort was young and relatively healthy, limiting generalizability, these results demonstrate the importance of investigating health-related worries when interpreting behaviors moving forward. in the weeks following the initiation of public health recommendations, public perceptions were overall favorable and participants reported adherence to mandates in the setting of worry about personal health and reluctance to seek emergency care for covid-19-related symptoms. we must consider patient fears and uncertainties regarding covid-19 to better understand how patients seek medical care. this work has not been presented at a meeting. j o u r n a l p r e -p r o o f ?cdc_aa_refval=https%3a%2f%2fwww.cdc.gov%2fcoronavirus%2f2019-ncov%2fprepare%2ftransmission.html. accessed advice for public amazon's mechanical turk: a new source of inexpensive, yet high-quality, data? delayed access or provision of care in italy resulting from fear of covid-19 reduced rate of hospital admissions for acs during covid-19 outbreak in northern italy the public's response to severe acute respiratory syndrome in toronto and the united states figure 1. adherence to harm-reduction strategies no financial support to disclose. key: cord-349355-k48s9sum authors: janssen, joris; kamps, marlijn j.a.; joosten, tamara m.b.; barten, dennis g. title: spontaneous pneumomediastinum in a male adult with covid-19 pneumonia date: 2020-07-30 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.066 sha: doc_id: 349355 cord_uid: k48s9sum spontaneous pneumomediastinum is a rare complication of viral pneumonia. here we report a case of a 52 year old male who presented with a spontaneous pneumomediastinum in covid-19 pneumonia, followed by a severe course of disease. we discuss the pathophysiological mechanisms underlying this association as well as its possible clinical implications as a marker of disease severity in covid-19. since december 2019, the covid-19 pandemic has evolved into a worldwide public health crisis, with up to 13 million confirmed cases and more than 570,000 deaths as of 15 july 2020 [1] . chest computed tomography (ct) has become an important instrument to diagnose covid-19, but it is also used for severity stratification and monitoring of disease. covid-19 causes typical radiographic features, including multifocal or peripherally distributed ground glass opacities with inter-or intralobular septal thickening (crazy paving appearance) [2] [3] [4] . here we present a case of spontaneous pneumomediastinum in covid-19 pneumonia, and discuss the possible mechanism underlying this association as well as clinical implications. a 52 year old male adult without significant medical history presented to the emergency department (ed) with a seven-day history of fever, dyspnea and a dry cough. his symptoms aggravated during the past days. on arrival at the ed, he did not have a severely ill appearance, but his peripheral oxygen saturation was 85% on ambient air. temperature was 38.6 °c, blood pressure 131/65 mmhg and pulse rate 86 bpm. laboratory tests revealed an elevated c-reactive protein concentration of 198 mg/l (reference: < 5 mg/l). complete blood count showed a leukocyte count of 8.0 x 10 9 /l (reference: 4-10 x 10 9 /l), with a relative left shift (9% band neutrophils [reference: < 5%]) and lymphopenia (5% [reference: 20-45%]). serum levels of d-dimer and ferritin were both raised at 1082 ug/l (reference: <500 ug/l) and 2636 ug/l (reference: 13-150 ug/l), respectively. non-contrast chest ct showed bilateral ground glass opacities and parenchymal consolidation. the patient was admitted to a designated covid-19 ward and treated with broad-spectrum antibiotics and chloroquine. three days later he developed respiratory failure and was transferred to the intensive care unit for mechanical ventilation. he was ventilated for 26 days, and after five more weeks of medical rehabilitation he was discharged home. follow-up chest ct obtained 14 weeks after initial presentation showed complete resorption of mediastinal air ( figure 2 ). spontaneous pneumomediastinum is a rare complication of viral pneumonia. it has been reported in severe acute respiratory syndrome (sars) virus infections, influenza and bacterial pneumonia with rare strains, such as p. jirovecii in immunocompromised patients [5] [6] [7] . spontaneous pneumomediastinum associated with covid-19 has occasionally been reported [8] [9] [10] . the presumed etiology is that the viral infection causes diffuse alveolar damage, which together with an increase in intra-alveolar pressure (as seen in intentional valsalva maneuver, such as coughing) leads to alveolar rupture. subsequently, this alveolar air circulates through the bronchovascular sheaths towards the mediastinum, following a negative pressure gradient. this pathophysiological mechanism is known as the macklin effect [11] . although spontaneous pneumomediastinum is generally considered a benign and self-limiting condition, its appearance in viral pneumonia may be of clinical significance as it has been previously suggested to be a potential indicator of disease severity. for instance, in sars patients it was observed that the development of a spontaneous pneumomediastinum was associated with significantly higher rates of intubation and mortality [12] . furthermore, a recent case series described three cases of covid-19 pneumonia that were complicated by spontaneous pneumomediastinum and pneumothorax, all of which were followed by a severe course of disease with fatal outcome [13] . although in our patient presentation with a spontaneous pneumomediastinum was associated with a severe course of covid-19 pneumonia as well, it is yet unclear to what extend this applies to other patients with covid-19 infection. in this context, it should be noted that in retrospective analysis selection bias might occur, assuming that in more severe cases more imaging studies are performed. j o u r n a l p r e -p r o o f therefore, further research is warranted to assess whether spontaneous pneumomediastinum is an indicator of disease severity in covid-19 pneumonia. spontaneous pneumomediastinum is a rare complication of covid-19 pneumonia and was associated with a severe course of disease in our patient. future studies are warranted to assess whether spontaneous pneumomediastinum is an indicator of disease severity in covid-19 pneumonia. correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases ct imaging features of 2019 novel coronavirus (2019-ncov) coronavirus disease 2019 (covid-19): role of chest ct in diagnosis and management spontaneous pneumomediastinum in h1n1 infection: uncommon complication of a common infection pneumomediastinum in a patient with pneumocystis jirovecii pneumonia clinical progression and viral load in a community outbreak of coronavirus-associated sars pneumonia: a prospective study spontaneous pneumomediastinum occurring in the sars-cov-2 infection mediastinal emphysema, giant bulla, and pneumothorax developed during the course of covid-19 pneumonia covid-19 with spontaneous pneumomediastinum. the lancet infectious diseases malignant interstitial emphysema of the lungs and mediastinum as an important occult complication in many respiratory diseases and other conditions: interpretation of the clinical literature in the light of laboratory experiment spontaneous pneumomediastinum in patients with severe acute respiratory syndrome. the european respiratory journal pneumomediastinum and spontaneous pneumothorax as an extrapulmonary complication of covid-19 disease the authors have no conflicts of interest relevant to this article to disclose. key: cord-254919-fi3inp67 authors: molina, melanie f.; al saud, ahad a.; al mulhim, abdullah a.; liteplo, andrew s.; shokoohi, hamid title: nitrous oxide inhalant abuse and massive pulmonary embolism in covid-19 date: 2020-05-16 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.023 sha: doc_id: 254919 cord_uid: fi3inp67 a patient presented to the emergency department with altered mental status and lower extremity weakness in the setting of nitrous oxide inhalant abuse and coronavirus disease-2019 (covid-19) infection. he subsequently developed hypotension and severe hypoxia, found to have a saddle pulmonary embolus (pe) with right heart strain requiring alteplase (tpa). j o u r n a l p r e -p r o o f laboratory investigations revealed elevated troponin t-hs of 70 ng/l, creatine kinase of 2,414 u/l, d-dimer of 7,386 ng/ml, lactate dehydrogenase of 424 u/l, procalcitonin of 0.10 ng/ml, lactate of 3.9 mmol/l, ferritin of 587 ug/l, homocysteine of 104.5 umol/l, and low vitamin b12 of <150 pg/ml. initial venous blood gas revealed a pco2 of 37 mmhg and a venous ph of 7.4. the patient was tested for covid-19 using polymerase chain reaction (pcr). although initial testing was negative, a second test was positive. subsequent hematology studies revealed the presence of lupus anticoagulant (lac). electrocardiogram revealed sinus tachycardia with incomplete right bundle branch block. lower-limb compression ultrasonography was positive for a nonocclusive deep venous thromboses (dvt) in the bilateral popliteal veins. the left internal jugular vein, which had been cannulated for central access, was also noted to subsequently develop thrombosis (video 1). bedside transthoracic echocardiography (tte) demonstrated right ventricular dilatation suggestive of right heart strain (video 2). given the high concern for pulmonary embolism with the above findings, computed tomography (ct) was performed and analysis of 183 confirmed covid-19 patients demonstrating an 11.5% death rate. of the patients who died, 86% had elevated d-dimers of ≥ 3 µg/ml, and 71% of them developed disseminated intravascular coagulation [3] . in a separate study by zhou et al, they also found that a d-dimer > 1 µg/ml was a predictor of mortality, with an 81% rate of mortality in those having an elevated d-dimer [2] . in a retrospective study of 449 patients with severe covid-19 pneumonia, 99 patients received heparin. the study showed a decrease in 28-day mortality among the subgroup of patients with a sepsis-induced coagulopathy (sic) score ≥4 or a d-dimer result that was 6 times the upper limit of normal [4] . recent guidelines have also suggested that an elevated d-dimer levels are j o u r n a l p r e -p r o o f associated with higher risk of requiring mechanical ventilation, icu admission, or death [5] . this patient's coagulopathy may have been secondary to a combination of covid-19 infection and n2o inhalant abuse leading to hyperhomocysteinemia. it is worth noting that while initial covid-19 pcr testing was negative, repeat testing was positive, which raises concerns regarding the sensitivity of the covid-19 pcr. in highly suspicious cases, two tests may be necessary to ensure adequate sensitivity. the role of the previously undetected lupus anticoagulant in the patient's coagulopathy is unclear and may have contributed as well. both covid-19 and nitrous oxide (n2o) could theoretically contribute to a hypercoagulable state. there are case reports illustrating a higher risk of vte associated with chronic n2o inhalant abuse [6, 7] . nitrous oxide leads to decreased vitamin b12 levels with chronic abuse, which leads to increased homocysteinemia by inhibition of methionine synthase [7] . clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy covid-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up pulmonary embolism and deep vein thrombosis caused by nitrous oxide abuse: a case report aortic arch thrombus caused by nitrous oxide abuse key: cord-350473-f47i7y5h authors: sen-crowe, brendon; mckenney, mark; elkbuli, adel title: covid-19 laboratory testing issues and capacities as we transition to surveillance testing and contact tracing date: 2020-05-27 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.071 sha: doc_id: 350473 cord_uid: f47i7y5h nan j o u r n a l p r e -p r o o f as of may 19 th , 2020, 11,834,508 covid-19 tests have been performed in the us resulting in 1,523,534 (12.9%) confirmed cases 1 . the actual number of infected americans is much larger. antibody seroprevalence testing in santa clara county, california, estimates those infected between 2.49%-4.16% implying actual infections 50-85-fold larger than confirmed cases 2 . another study concluded that undiagnosed covid cases represent the infection source of 79% of documented cases 3 . accurate testing will be crucial to controlling and understanding this pandemic. estimation relies on testing kit accuracy (sensitivity/specificity). low sensitivity will underestimate disease prevalence, while low specificity will overestimate. 2 testing comes in two broad types, testing for nasopharyngeal viral rna and serologic testing for antibodies, which occur in response to the disease. rna testing is done with polymerase chain reaction (pcr) is cost-effective, easy to perform, and now available 4 . however, the pcr test has accuracy issues. sensitivity of fda-approved viral rna tests range from 63%-95% (table 1) [5] [6] [7] [8] . sensitivity of rna tests is dependent on the site of specimen collection. sensitivity was highest in bronchioalveolar lavage (93%), then sputum (73%), nasal swab (63%), feces (29%) and blood (1%). 5 another study found that patients with pneumonia often have negative nasopharyngeal samples, but positive lower airway samples 9 . the sensitivity of pcr tests have been estimated at 71%, resulting in ~30% of infected patients having a negative finding. another drawback is the presence of viral rna does not mean the virus is live, therefore, detection does not necessarily mean the virus can be transmitted 9 . rna-based tests are limited to the setting of acute illness. saliva-based tests offer promising results as a non-invasive and non-aerosol generating method of specimen collection 10 . compared to nasopharyngeal tests, saliva specimens have high sensitivity (84.2% 10 ) and can be self-administered. 10 one study reported greater sensitivity in saliva samples as compared to nasopharyngeal swabs and less variability. 11 reduced variability in samples taken from self-administered tests is helpful for mass testing because it preserves collection reliability and allows patients to send in their own samples from the comfort of their home. the second type of test is serologic, which detects immunoglobulins (igg and igm) specific for sars-cov-2 and provides an estimation of population virus exposure 4 . one drawback of serologic testing is the lag period between symptoms and antibody formation-one analysis found patients do not begin to seroconvert until 11-12 days post-symptom onset 12 .the sensitivity and specificity of fda-approved serologic tests ranges from 61.1%-98% and 90%-100% 13 . many fda-approved serologic tests have high sensitivity and specificity. for example, cellex inc. developed a rapid diagnostic test with 93.8% sensitivity and 95.6% specificity. bio-rad manufactured an elisa test with sensitivity and specificity of 98% and 99%, respectively (table 1) 13 . there are also clinical associations with confirmed covid-19 patients. an analysis of 119 patients with covid-19 at from wuhan university revealed an association with low urine specific gravity and increased ph 14 . in addition, the urine glucose and proteinuria correlated with severe/critical cases compared to mild/moderate 4 . the results imply that certain urinalysis profiles can be used to predict the severity of disease and possibly testing of asymptomatic patients that could be quarantined until a definitive test can be completed 14 . to address the development of a reliable test, the department of health & human services (hhs) provided funding for the development of simplexa covid-19 direct assay and to qiagen to accelerate development of their rps2 test 15 . additionally, hhs is purchasing the id now covid-19 rapid point-of-care test (abbott diagnostics scarborough inc.) for public health labs (table 1) 16 . the fda is issuing emergency use authorizations to expedite distribution 17 . states have differing amounts of laboratories authorized for testing ( figure 1 ). the targeted distribution of tests to areas of high density (figure 1-black diamonds) is paramount to ensure that resources are not undersupplied. the road back to normalcy is contingent on accurate tests, allowing suppression of spread. when a localized outbreak occurs, it will be important to have reliable testing methods to promptly contain it. random serologic testing can be used to surveil populations at high-risk for an outbreak. pcr tests can be used to assess those with active infection who may be asymptomatic. targeted distribution of tests needs to be to areas where covid is more prevalent and where people are at higher risk. in addition to distribution, the quality of the tests require improvement. many prospective tests in development report promising results in under 60 minutes, such as mammoth bioscience's crispr-based lateral flow assay (sensitivity:90%, specificity:100%) and united biomedical's kit (sensitivity:100%, specificity:100%) (table 1) . 13, 18 in the present era, technology allows diagnostics to be readily available. understanding the current disease state in communities' plays a role in the acceptance of control measures that require individual actions. now is the time to ensure systematic and coordinated efforts between the clinical, commercial and public sectors to leverage the power of testing to address the pandemic at our door. covid-19 map. johns hopkins coronavirus resource center covid-19 antibody seroprevalence diagnostic testing for severe acute respiratory syndrome-related coronavirus-2: a narrative review from mitigation to containment of the covid-19 pandemic: putting the sars-cov-2 genie back in the bottle detection of sars-cov-2 in different types of clinical specimens smart detect sars-cov-2 rrt-pcr kit. inbios covid-19 rt-digital pcr detection kit respiratory sars-cov-2 panel instructions for use (handbook) report from the american society for microbiology covid-19 international summit saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease-2019 (covid-19): a cross-sectional study saliva is more sensitive for sars-cov-2 detection in covid-19 patients than nasopharyngeal swabs the promise and peril of antibody testing for covid-19 serology-based tests for covid-19. johns hopkins -center for health security the value of urine biochemical parameters in the prediction of the severity of coronavirus disease 2020;/j/cclm.ahead-of-print hhs funds development of covid-19 diagnostic tests. u.s. department of health & human services territorial and tribal public health labs with covid-19 rapid point-of-care test covid-19) -laboratory capacity crispr-cas12-based detection of sars-cov-2 key: cord-334416-4tslee57 authors: sen-crowe, brendon; mckenney, mark; elkbuli, adel title: social distancing during the covid-19 pandemic: staying home save lives date: 2020-04-02 journal: am j emerg med doi: 10.1016/j.ajem.2020.03.063 sha: doc_id: 334416 cord_uid: 4tslee57 nan the severity of the covid-19 outbreak is the greatest public health threat caused by a respiratory virus since 1918. according to the imperial college, 2.2 million americans could die if we do not mitigate the spread of infection [1] . with the incidence of covid-19 increasing, it may only be time before the healthcare system becomes overwhelmed and forces physicians to triage treatment among critically ill patients. without an intervention, it is likely that there will be more seriously ill people than we have the resources to care for [1] . the rate of covid-19 infection is largely determined by its reproductive number (r 0 )-the number of secondary infections produced by an infected person. if the r 0 is n1, infections will continue to spread. if r 0 is ≤1 the infection will eventually diminish. the r 0 of covid-19 is estimated at 1.3-6.5, with an average of 3.3 [2] . r 0 is affected by a number of factors including the innate properties of the virus, and the amount/ duration of contact people have with each other [3] . although we cannot influence biological properties of the virus, we can change the amount of contact we have with each other via a phenomenon known as social distancing. social distancing is the practice of increasing the space between people in order to decrease the chance of spreading illness. according to the cdc, spacing of 6 ft away decreases the spread of covid-19 [4] . individual actions include working remotely, avoiding public transportation, and staying home if you suspect you have been exposed and/or are symptomatic [5] . community-wide measures include transition to online teaching, businesses temporarily closing, and the widespread engagement of telecommunication [6] . multiple states including washington state, california, and new york are resorting to statewide home orders being issued to minimize contact [7] [8] [9] . nationwide measures taken to minimize contact with potentially infected individuals include cancelling travel from china and europe [10] . it is likely that additional action will be taken with suspension of domestic air travel on the list. according to a large study performed in china, younger individuals are more likely to be asymptomatic when infected and could be unaware they are putting others at risk [11] . of noteworthy importance is the risk of transmitting infection to the elderly, particularly those over the age of 60 [12] . the severity of illness is much more dire in this population with a strong association between in-hospital death and older age [13] . for this reason, it is essential that contact is limited not only to ensure personal safety, but also to prevent the spread of disease to others who are at high risk for developing severe complications. social distancing also plays a role in lessening the burden imposed on the healthcare system. in the absence of any intervention, there would be a rapid rise in the number of cases that could overwhelm the healthcare system's capacity, and force physicians to treat some patients over others. if 200,000 people became critically ill in the same week, it would overwhelm the b100,000 icu beds [14] . moreover, it is likely that many of these patients would require a full-feature ventilator, exceeding the 62,000 available [15] . on the other hand, if this same situation occurred over the course of several weeks, it would be more manageable. social distancing has the potential to slow the rate of infection and reduce the peak of incidence, and then fewer critically ill patients would need care on any one day. the peak incidence could be reduced to a level the healthcare system is equipped to adequately respond to and save thousands of lives that would otherwise be left without treatment. delaying the peak to a later time-period could be beneficial. delaying the peak incidence to the summer holds potential for healthcare facilities to dedicate more resources to those ill with covid-19. many of the resources used for serious cases of influenza are also required for severe cases of covid-19 and stalling the peak incidence of cases to the summer when the majority of influenza cases have resolved may lend more resources to these patients. in the end, this improves the healthcare system's ability to treat those in critical condition without the need to ration. it is too late to stop covid-19; the importance of slowing the infection cannot be understated. with the vast amount of cases identified in the us, resources are becoming scarce. concern in public health has often been about the shortage of physicians-rarely do we consider if a ventilator will be available if you become critically ill. social distancing is a realistic solution that all individuals can take part in to reduce the risk of infection while increasing available resources to critically ill patients, during this pandemic. we can still practice physical distancing while remaining connected socially, emotionally, and spiritually. we can do this together to defeat the covid19 pandemic and continue moving forward towards a brighter future for our current and future generations. impact of non-pharmaceutical interventions (npis) to reduce covid-19 mortality and healthcare demand. imperial college of london the reproductive number of covid-19 is higher compared to sars coronavirus complexity of the basic reproduction number (r0) transmission of coronavirus disease 2019 (covid-19) personal npis: everyday preventative actions. center for disease control and prevention community npis: everyday preventative actions. center for disease control and prevention stay home, stay healthy" order governor cuomo signs the 'new york state on pause' executive order. governor andrew m governor gavin newsom issues stay at home order. office of governor gavin newsom proclamation-suspension of entry as immigrants and nonimmigrants of certain additional persons who pose a risk of transmitting 2019 novel coronavirus. the white house epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in china covid-19) -united states clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study american hospital association mechanical ventilators in us acute care hospitals key: cord-336005-nm34bfsl authors: mahan, keenan; kabrhel, christopher; goldsmith, andrew j. title: abdominal pain in a patient with covid-19 infection: a case of multiple thromboemboli date: 2020-05-26 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.054 sha: doc_id: 336005 cord_uid: nm34bfsl the novel coronavirus sars-cov-2 (covid-19) pandemic has created diagnostic uncertainty with regards to distinguishing this infection from pulmonary embolism (pe). although there appears to be an increased incidence of thromboembolic disease in patients with covid-19 infection, recommendations regarding anticoagulation are lacking. we present the case of a 61-year-old woman with clinically significant venous and arterial thromboemboli in the setting of covid-19 infection requiring tissue plasminogen activator (tpa). the novel coronavirus pandemic has had widespread global impact with over 3.3 million cases and 238,000 deaths as of early may. [1] many covid-19 patients requiring hospitalization have symptoms indistinguishable from conditions such as pulmonary embolism (pe). [2, 3] to further complicate the clinical situation, many patients have d-dimer elevations and are at increased risk of thromboembolic complications. [4] [5] [6] [7] [8] [9] [10] [11] [12] given the virulence of covid-19, further radiological testing beyond chest radiography (cxr) is debated. in addition, there is no clear guidance as to whether anticoagulation should be initiated for emergency department (ed) patients with presumed covid-19 and elevated d-dimer. we thereby present a patient who was found to have significant venous and arterial thromboembolic disease in the setting of covid-19 infection. a 61-year-old woman with a pertinent medical history of type ii diabetes mellitus presented to the ed with three days of dry cough and one day of non-radiating abdominal pain. she reported sharp, severe, periumbilical pain which began acutely that morning. on review of symptoms she denied nausea, vomiting, diarrhea as well as fevers, shortness of breath and chest pain. of note, her husband was diagnosed with covid-19 the day before. in the ed, her initial vital signs were notable for tachypnea at 34 respirations per minute, hypoxemia to 87% on room air, tachycardia to 112 beats per minute, and a blood pressure of 144/83. her hypoxemia improved to 96% with 4l/min of supplemental oxygen via nasal cannula. on exam, the patient was speaking in full sentences and had periumbilical tenderness without rebound or guarding. based on her symptoms we ordered laboratory work, a chest x-ray (cxr), a covid-19 reverse transcription polymerase chain reaction (rt-pcr) test, and a computerized tomography (ct) scan of the abdomen and pelvis. the patient's cxr demonstrated bilateral peripheral opacities consistent with covid-19 infection ( figure 1 ) and her d-dimer returned elevated at 8,264ng/ml. based on the patient's hypoxemia, persistent tachycardia, and marked d-dimer elevation, we ordered a ct pulmonary angiogram which revealed multiple filling defects in the thoracic and abdominal aorta representing thromboemboli as well as diffuse bilateral ground glass opacities in the lungs (figure 2) . the ct scan also revealed a right ventricular (rv) filling defect concerning for thrombus, which was later confirmed on transthoracic echocardiogram ( figure 3 ). her ct abdomen/pelvis revealed no additional acute pathology. we initiated therapeutic unfractionated heparin and admitted the patient. within 24 hours, she developed worsening dyspnea and hypoxemia and received tissue plasminogen activator to treat her rv clot-in-transit and presumed pe. the covid-19 rt-pcr returned positive the same day. in our patient, an elevated d-dimer led us to order a ct pulmonary angiogram that found multiple venous and aortic thromboemboli. in covid-19, elevated d-dimer levels are common and thought to be secondary to the inflammatory response causing a hypercoagulable state. [3, 10, 13] studies suggest d-dimer levels >5x normal are associated with poor outcomes, including thromboembolic complications. [4, [6] [7] [8] 14, 15] however, no guidance regarding further imaging and anticoagulation is provided. covid-19 map -johns hopkins coronavirus resource center clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study hematological findings and complications of covid-19 clinical features and treatment of covid-19 patients in northeast chongqing critically ill covid-19 infected patients exhibit increased clot waveform analysis parameters consistent with confirmation of the high cumulative incidence of thrombotic complications in critically ill icu patients with covid-19: an updated analysis pulmonary embolism or pulmonary thrombosis in covid-19? is the recommendation to use high-dose heparin for thromboprophylaxis justified? comparison of clinical and pathological features between severe acute respiratory syndrome and coronavirus disease zhonghua jie he he hu xi za zhi incidence of thrombotic complications in critically ill icu patients with covid-19 clinical course and risk factors for mortality of j o u r n a l p r e -p r o o f adult inpatients with covid-19 in wuhan, china: a retrospective cohort study anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy isth interim guidance on recognition and management of coagulopathy in covid-19 covid-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents diagnosing centrally located pulmonary embolisms in the emergency department using point-of-care ultrasound j o u r n a l p r e -p r o o f key: cord-352656-hpuhjbki authors: cohen, brett a.; wessling, emily g.; serina, peter t.; cruz, daniel s.; kim, howard s.; mccarthy, danielle m.; loftus, timothy m. title: emergency department operations in a large health system during covid-19 date: 2020-06-02 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.097 sha: doc_id: 352656 cord_uid: hpuhjbki • the initial covid-19 pandemic led to decreased ed volumes across a health system. • decreased ed volumes during the covid-19 pandemic led to improved operations metrics. • hospital decompression led to decreased boarding times during the covid-19 pandemic. the coronavirus disease 2019 (covid-19) pandemic has strained healthcare systems through increased care complexity, need for staff and patient safety, and surges in patients suspected or known to be infected with severe acute respiratory syndrome-coronavirus 2 (sars-cov2). previous infectious disease outbreaks and natural disasters have altered clinical operations and ed performance in different manners depending on the disaster type and duration. during the 2009 h1n1 influenza pandemic, total ed patient visits increased, 1 and measures of ed performance such as patient length of stay (los), waiting time, left without being seen (lwbs) and boarding time were negatively affected. 2,3 following a severe wildfire in san diego, ed volumes decreased while rates of admission and lwbs increased. 4 immediately following hurricane harvey, visits to free-standing eds in houston increased. 5 conversely, after hurricane sandy, ed visits in new york plummeted but quickly returned to pre-disaster rates. 6 this retrospective review examines ed volumes and operational metrics of a health system in the chicagoland area from january 1, 2020 to april 22, 2020. the seven hospitals analyzed were categorized by annual ed volumes and include: one very-high volume urban academic ed, one high-volume suburban community ed, and five average to low-volume community sites ( table 1 ). the following operational metrics were collected: median daily visits, covid-19 specific j o u r n a l p r e -p r o o f visits, patients lwbs, door to diagnostic evaluation by a qualified medical professional ("doorto-doc" time), hospitalization rate, decision to admit to ed departure (boarding time), and median ed los. the study described three time periods determined by public health messaging and initial local cases: pre-covid-19 (1/1/2020 -3/3/2020), response (3/4/2020 -3/24/2020), and post-response (3/25/2020 -4/22/2020) (figure 1). operational metrics were compared using the wilcoxon rank sum test. the institutional review board approved this study. compared to the pre-covid time period, median daily ed volume decreased in the postresponse time period by 37.9%, 39.0% and 41.9% at very-high volume, high-volume and average to low-volume hospitals respectively (all p<0.001) ( table 2 ). the median percentage of visits related to covid-19 increased to 44.4%, 27.3%, 17.4% respectively ( table 2 ). the evaluation of operational metrics revealed the very high-volume urban academic ed experienced the greatest improvements, with lwbs, ed los, boarding time, and door-to-doc time decreasing by 89.5%, 36.1%, 49.4% and 83.8% respectively (all p<0.001) ( table 3) . median daily and covid-specific visits, median ed los, and waiting time (door-to-doc) are also displayed graphically ( figure 1 ). this analysis describes how a single pandemic can have a differential impact on individual hospitals, even within the same region and health system. despite the higher proportion of covid-related encounters, the very high-volume center saw greatest improvements in operational performance metrics. this is consistent with previous studies that have identified patient acuity and ed volume as strong predictors of ed performance. 7 disaster preparedness efforts targeted at hospital decompression and reduction of ed demand, such as cancellation of elective surgeries, expansion of icu capacity and dedicated outpatient covid-19 testing areas may have the greatest impact at the more congested, urban academic center. prior studies have examined changes in ed volumes and associated operational measures during disasters. in contrast to volume surges seen in nyc urban eds by a mean of 60.7% during the 2009 h1n1 outbreak 8 , during the covid-19 pandemic we describe decreased daily volumes by 37.9% in the urban ed and 41.9% in the community eds. during the same h1n1 outbreak atlanta experienced ed overcrowding as a result of the pandemic 9 , whereas in this analysis, an improvement was seen in ed crowding metrics. these findings are, however, similar to those during the initial stages of the 2003 sars epidemic in hong kong and hurricane sandy in nyc, when mean daily ed patient visits significantly decreased. 6, 10 evaluating the complex and temporal contributing factors driving these similarities and differences is beyond the scope of this analysis; however, hypothesized factors include the novelty of the disease, media coverage, presence of social distancing mandates, and messaging about when and where to seek care. there are several study limitations. the analysis of a single health system limits generalizability to other regions and disasters. specific conclusions on the nature of the ed visits other than those related to covid-19 complaints cannot be drawn based on aggregate data. the retrospective, descriptive nature of this analysis limits the conclusions on causation or singular associations of variables. the above data demonstrate a trend of decreased ed patient visits across a single health system during the initial stages of the covid-19 pandemic, in conjunction with greater improvements in ed operational metrics observed at a large urban academic center compared to smaller community hospitals within the same health system. although further data are needed to best characterize these patterns nationally, this early work points to a unique volume and metric impact in comparison to previous pandemics and natural disasters. j o u r n a l p r e -p r o o f figure 1 . graphical representation of total number of patient encounters (weekly), covid-19 related encounters (weekly), and median ed length of stay (hours) and door to doc time (hours). hospitals were categorized by annual ed volumes into very-high volume (80-100k), highvolume (60-80k) and average to low-volume (<60k). noted are key dates including first case of covid-19 in illinois (1/24/2020), first case of covid-19 in health system (3/4/2020), who declaration of global pandemic (3/11/2020) and state of illinois stay at home order (3/21/2020). j o u r n a l p r e -p r o o f j o u r n a l p r e -p r o o f -89.5%*** -50.0%* -100.0%* 14.1%*** 9.9%* 13.30% -36.1%*** -22.5%*** -14.7%*** -49.4%*** -10.0%* -20.9%*** -83.8%*** -62.9%*** -61.1%*** *p<0.05, **p<0.01, ***p<0.001 figure 1 impact of seasonal and pandemic influenza on emergency department visits emergency department performance measures updates: proceedings of the 2014 emergency department benchmarking alliance consensus summit anatomy of a demand shock: quantitative analysis of crowding in hospital emergency departments in victoria, australia during the 2009 influenza pandemic san diego wildfire impact on the emergency department of the university of california, san diego hospital system freestanding emergency department visits and disasters: the case of hurricane harvey geographic distribution of disaster-specific emergency department use after hurricane sandy in new york city volume-related differences in emergency department performance clinical advisory committee h1n1 working group nwycie. health information exchange, biosurveillance efforts, and emergency department crowding during the spring 2009 h1n1 outbreak a survey of emergency department 2009 pandemic influenza a (h1n1) surge preparedness impact of sars on an emergency department in hong kong key: cord-341527-03rh966o authors: stockton, john; kyle-sidell, cameron title: dexmedetomidine and worsening hypoxemia in the setting of covid-19: a case report date: 2020-05-27 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.066 sha: doc_id: 341527 cord_uid: 03rh966o emergency department management of hypoxemia in the setting of covid-19 is riddled with uncertainty. the lack of high-quality research has translated to an absence of clarity at the bedside. with disease spread outpacing treatment consensus, provider discretion has taken on a heightened role. here, we report a case of dexmedetomidine use in the setting of worsening hypoxemia, whereby oxygenation improved and intubation was avoided. well known pharmacologic properties of the drug, namely the lack of respiratory depression and its anti-delirium effects, as well as other possible physiologic effects, suggest potential benefit for patients being managed with a delayed intubation approach. if dexmedetomidine can improve compliance with non-invasive oxygen support (the current recommended first-line therapy) while promoting better oxygenation, it may also decrease the need for mechanical ventilation and thus improve mortality. as of this writing, there have been over 1,300,000 confirmed cases of covid-19 and 80,000 deaths in the united states [1] . while early intubation was the initial recommended strategy for covid-19 hypoxemia, a large case series in the us as well as data coming out of britain, china, and italy suggests a high mortality for patients requiring invasive ventilation [2] . the national institute of health now recommends high flow nasal cannula (hfnc) as first line oxygen support [3] . the following case addresses the management of one patient on hfnc, with specific reference to dexmedetomidine. a 58-year-old female with hypertension presented to a new york city emergency department for shortness of breath for one day in the setting of known covid-19 diagnosed one week prior. initial vital signs revealed an spo2 of 95% on room air. on examination, the patient was tachypneic. her chest x-ray showed pulmonary infiltrates consistent with covid-19. initially placed on a non-rebreather mask, the patient's spo2 gradually dropped and she was started on hfnc (40l and 88% fio2). on day 2 1 , oxygen requirements continued to increase and her hfnc was titrated up to 100% at 60l, with a non-rebreather placed over it. on day 8 (day 15 of illness by symptomatology), spo2 worsened from 92% to 84%, despite j o u r n a l p r e -p r o o f maximal oxygen support. the patient appeared uncomfortable, intermittently attempting to displace her oxygen devices. a dexmedetomidine infusion was initiated, after which saturations increased, she appeared more comfortable, and she remained compliant with her oxygen devices. her spo2 remained in the 86% to 100% range and on day 12, she was transitioned from hfnc to nasal cannula (6l) and admitted. at the time of this writing, she remains on nasal cannula and is doing well (ambulating, tolerating a regular diet and with a normal mental status). severe covid-19 pulmonary disease is characterized by hypoxemia and requires a multimodal approach. our patient received the standard medical therapy endorsed by our department at the time of her care: supplemental oxygen, azithromycin, anticoagulation and corticosteroids. she was placed in trials for tocilizumab and convalescent plasma and received chest physical therapy and awake intermittent proning. however, there are several reasons to believe dexmedetomidine contributed significantly to her course. as figure 1 demonstrates, during the first seven days her spo2 generally remained > 90%. nevertheless, her chart notes worsening tachypnea, titration of hfnc to maximal settings and eventually requiring a non-rebreather mask placed over her hfnc. as spo2 dropped, she became agitated and at risk of dislodging her oxygen devices. intubation was strongly j o u r n a l p r e -p r o o f considered. however, with departmental preference toward delayed intubation 2 , consensus developed to administer dexmedetomidine instead. after, our patient's spo2 increased from 84% to 100%, with no other intervention taking place at the time 3 . given the context of gradually worsening hypoxemia, timing of administration, subsequent improvement in spo2 and observed change in mental status (from agitated to calm), dexmedetomidine appeared to play a significant role. the patient avoided intubation, now has a stable spo2 on nasal cannula and is not in multi-system organ failure, a significant victory considering the alternative. the pharmacokinetics of dexmedetomidine make it ideal in nonintubated covid-19 patients. it has a minimal effect on respiratory drive, a rapid onset and elimination and is easily titratable [4] . its side effect of bradycardia appears to be well tolerated. on a behavioral level, patients with worsening hypoxia are often very anxious and prone to agitation. this becomes especially dangerous when fully dependent on supplemental oxygen, where acute decline from dislodgement of support devices is always a concern. dexmedetomidine has been shown in randomized controlled trials to decrease agitated delirium in critically ill patients [5] . this benefit is likely amplified in elderly populations, who have higher mortality and baseline conditions that predispose them to delirium and noncompliance with hfnc. dexmedetomidine may promote oxygenation on a physiologic level as well. the mechanism of hypoxemia in covid-19 is thought to be disrupted pulmonary vasoregulation due to viral induced endothelial damage of pulmonary capillaries and ensuing v/q mismatch [6] . recent studies suggest dexmedetomidine may enhance hypoxic pulmonary vasoconstriction, improve ventilation/perfusion ratio and consequently improve oxygenation [7] . the uncertainty of covid-19 has led to varying approaches in treatment which have yet to be validated and are not without their own risks 4 . in this case, we believe dexmedetomidine helped one patient avoid mechanical ventilation by improving compliance with non-invasive ventilation and promoting better oxygenation. whether that was primarily due to behavioral or physiologic changes induced by the drug is unknown. however, this case suggests that the unique pharmacologic properties of dexmedetomidine may help decrease the need for mechanical ventilation, thereby reducing mortality. in the face of this novel and complicated disease, the suggestion of such benefit is deserving of further investigation. 2 informed by recent experience during the pandemic. 3 average saturations after dexmedetomidine were 93% compared to 92% prior. during this time, occasional increases in agitation (correlated with events such as bowel movements) were accompanied by decreases in saturation, likely lowering the overall average. 4 delaying intubation, for example, risks suboptimal intubation conditions should the patient continue to progress in their disease, and certainly requires heightened vigilance while a patient remains on life sustaining non-invasive ventilation. cases in the us presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area 19 treatment guidelines. care of critically ill patients with covid-19 alpha-2 adrenergic receptor agonists: a review of current clinical applications the effect of dexmedetomidine on delirium and agitation in patients in intensive care: systematic review and meta-analysis with trial sequential analysis management of covid-19 respiratory distress evaluation of the effects of dexmedetomidine infusion on oxygenation and lung mechanics in morbidly obese patients with restrictive lung disease key: cord-330704-4piesfxu authors: avdeev, sergey n.; yaroshetskiy, andrey i.; tsareva, natalia a.; merzhoeva, zamira m.; trushenko, natalia v.; nekludova, galina v.; chikina, svetlana yu title: noninvasive ventilation for acute hypoxemic respiratory failure in patients with covid-19 date: 2020-10-01 journal: am j emerg med doi: 10.1016/j.ajem.2020.09.075 sha: doc_id: 330704 cord_uid: 4piesfxu aim: noninvasive ventilation (niv) is known to reduce intubation in patients with acute hypoxemic respiratory failure (ahrf) [1]. we aimed to assess the outcomes of niv application in covid-19 patients with ahrf. materials & methods: in this retrospective cohort study, patients with confirmed diagnosis of covid-19 and ahrf receiving niv in general wards were recruited from two university-affiliated hospitals. demographic, clinical, and laboratory data were recorded at admission. the failure of niv was defined as intubation or death during the hospital stay. results: between april 8 and june 10, 2020, 61 patients were enrolled into the final cohort. niv was successful in 44 out of 61 patients (72.1%), 17 patients who failed niv therapy were intubated, and among them 15 died. overall mortality rate was 24.6%. patients who failed niv were older, and had higher respiratory rate, paco(2), d-dimer levels before niv and higher minute ventilation and ventilatory ratio on the 1-st day of niv. no healthcare workers were infected with sars-cov-2 during the study period. conclusions: niv is feasible in patients with covid-19 and ahrf outside the intensive care unit, and it can be considered as a valuable option for the management of ahrf in these patients. the novel coronavirus disease 2019 (covid-19) outbreak that began in 2019 and spread rapidly across the world has been observed to cause viral pneumonia and acute hypoxemic respiratory failure (ahrf) [2] . for patients who are unresponsive to conventional oxygen therapy, high-flow nasal cannula (hfnc) oxygen, noninvasive ventilation (niv) or invasive mechanical ventilation (imv) may be administered [3] . several studies suggested high mortality for patients with covid-19-associated ahrf who received imv [4] , raising the concern that these patients may be particularly vulnerable to ventilator-induced lung injury [5] . noninvasive oxygenation strategies that could at least safely spare patients of imv could be of enormous importance. however, there were major concerns that hfnc or niv may create risks for health care workers (hcws) because of sars-cov-2 transmission via aerosols [6] while the data on the efficacy of noninvasive modalities in covid-19-associated ahrf are still limited [6] [7] [8] . the aim of this study was to assess the outcomes of niv application in covid-19 patients with ahrf. this retrospective cohort study was conducted in covid-19 care units of two university-affiliated hospitals between april 8 and june 10, 2020. the study was approved by the local ethics committee (approval number [16] [17] [18] [19] [20] . as this was a retrospective study, the requirement for informed consent was waived. we analyzed all patients aged ≥ 18 years with the laboratory-confirmed sars-cov-2 infection admitted to the general wards (outside intensive care units) for ahrf. the inclusion criteria were the need for oxygen greater than 6 l/min to maintain oxygen saturation (spo 2 ) above j o u r n a l p r e -p r o o f 92% and symptoms of respiratory distress (dyspnea, tachypnea, and activation of respiratory accessory muscles). the exclusion criteria were as follows: the need for immediate endotracheal intubation (eti), niv duration less than 60 minutes, chronic respiratory diseases (chronic obstructive pulmonary disease, obesity hypoventilation syndrome, etc), and unstable hemodynamics (requiring vasopressor support and/or lifethreatening heart rhythm abnormalities). all included patients were managed in isolated neutral pressure rooms. demographic data, comorbidities and clinical laboratory data were recorded at admission, and respiratory parameters were recorded before niv start and on the 1st day of niv. we used niv ventilators equipped with air-oxygen blender (trilogy 202, philips respironics, usa) and non-vented oronasal masks; the expiratory limb of the circuit was equipped with an antimicrobial filter. the primary niv mode was the continuous positive airway pressure (cpap), the pressure was initially set at 10 cm h2o and then adjusted according to spo 2 and clinical tolerance. a pressure support ventilation (psv) was considered over cpap in patients who showed respiratory acidosis (ph<7.35), tachypnea >30/min or a vigorous activity of respiratory accessory muscles. fio 2 was adjusted to maintain the arterial oxygen saturation of more than 92% during niv. patients with bilateral posterior infiltrates were placed in the prone position for at least 8 hours a day. the failure of niv was defined as intubation or death during the hospital stay. the ng/ml, p<0.0001) ( table 1) table 1) . d-dimer was the best predictor of niv failure with the area under the roc curve of 0.82 (95% ci 0.64-1.00), p=0.002, sensitivity 82% and specificity 80% for d-dimer level > 1190 ng/ml). all hcws who were exposed to niv patients used appropriate personal protection equipment (ppe) composed of ffp2/ffp3 masks, eye and head protections, disposable protective suits, gloves, and overshoes and nobody of hcws was infected with sars-cov-2 during the study period. this study suggests that the use of niv is feasible in acute hypoxemic respiratory failure in patients with covid-19 outside intensive care unit and can be considered as an effective means to improve oxygenation in patients not responding to conventional oxygen therapy. about 28% of our covid-19 patients with ahrf failed niv and required eti and imv with an associated mortality of 88%, compared with 0% when niv succeeded. our results are in accordance with recent reports on the use of niv in covid-19-associated ahrf, where the niv failure rate varied from 23% to 45% [7] [8] [9] . no significant difference between the success and failure groups in baseline pao 2 /fio 2 was found in our study, although a low baseline pao 2 /fio 2 was shown to be a risk factor of niv failure in several studies [10] . interestingly, the median pao 2 /fio 2 values in our patients were lower than those from a cohort study of mechanically ventilated [11] . we identified elevated d-dimer levels as a strong predictor of niv failure. in a study by wang et al, describing a nationwide cohort of critically ill covid-19 patients in china, elevated ddimer (>1.5 mg/l) at admission was also an indicator of increased possibility of imv requirement [12] . it was shown that d-dimer elevation in covid-19 was associated with the progression of the disease [13] , so, progressive underlying processes can predispose to prolonged respiratory support and niv failure [14] . we found that patients who failed niv had some important characteristics of gas exchange. this concerns minute ventilation and ventilation ratio during niv, which in general may be associated with increased alveolar dead space and impaired carbon dioxide clearance. higher minute ventilation in patients with niv failure was due to slightly higher tidal volume and higher respiratory rate, which, of course, may increase the risk of lung injury [15] . the time to niv failure and eti had a very wide range that can be explained by different time from disease onset to niv start, different volumes of lung injury and different rate of disease progression. no healthcare workers helping to treat the patients on niv were infected with sars-cov-2 during the study period. these data could be confirmed from other studies. in an observational study by oranger et al. the proportion of hcws contaminated by sars-cov-2 was similar before and after the implementation of cpap in the management of covid-19 patients (6% vs 10%) [7] . in a recent study of gaeckle et al. there was no observed increase in the concentration of aerosolized viral particles with the use of niv or hfnc when compared to breathing room air [16] . so, with appropriate ppe, the hcw infections can be avoided even caring for patients with niv. j o u r n a l p r e -p r o o f this study has several limitations. first, its retrospective design is susceptible to selection bias, however, all clinical and laboratory parameters were collected prospectively. second, the small study population precludes subgroup analyses and extensive multivariate analysis due to the limited size of events. third, our study is a single-center study (although it was performed in two university-affiliated hospitals) with respect to practice of niv, and so might not be generalizable to other centers. in summary, we have shown that niv is feasible in patients with covid-19 with acute hypoxemic respiratory failure outside the intensive care unit, and it can be considered as a valuable option for the management of ahrf in these patients. no healthcare workers helping to treat the patients on niv were infected with sars-cov-2 during the study period. bmi, body mass index; pao 2 /fio 2 , arterial oxygen tension to inspired oxygen fraction ratio; crp, c-reactive protein; wbl, whole blood leucocytes; v t , tidal volume; ibw, ideal body weight. association of noninvasive oxygenation strategies with all-cause mortality in adults with acute hypoxemic respiratory failure: a systematic review and meta-analysis clinical characteristics of coronavirus disease 2019 in china surviving sepsis campaign: guidelines on the management of critically ill adults presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area high incidence of barotrauma in patients with covid-19 infection on invasive mechanical ventilation epidemiology of and risk factors for coronavirus infection in health care workers: a living rapid review continuous positive airway pressure to avoid intubation in sars-cov-2 pneumonia: a two-period j o u r n a l p r e -p r o o f journal pre-proof retrospective case-control study helmet cpap treatment in patients with covid-19 pneumonia: a multicenter, cohort study feasibility and clinical impact of out-of-icu non-invasive respiratory support in patients with covid-19 related pneumonia effectiveness and predictors of success of noninvasive ventilation during h1n1 pandemics: a multicenter study respiratory pathophysiology of mechanically ventilated patients with covid-19: a cohort study patients with mechanical ventilation: a nationwide study in china risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in wuhan, china noninvasive ventilation for acute hypoxemic respiratory failure/ards -is there a role? ventilator-related causes of lung injury: the mechanical power aerosol generation from the respiratory tract with various modes of oxygen delivery key: cord-338863-0jlp9lb4 authors: huecker, martin; shreffler, jacob; danzl, daniel title: covid-19: optimizing healthcare provider wellness and posttraumatic growth date: 2020-08-27 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.066 sha: doc_id: 338863 cord_uid: 0jlp9lb4 nan sars-2003, h1n1 influenza 2009, mers-2012, and now the covid-2019 pandemic disrupt society in unpredictable ways (1) . responses to covid-19 include remote schooling, limited gatherings and suspension of economic activity (2) . major stressors lead to diverse outcomes, negative and positive. individuals who lose loved ones, suffer intimate partner violence, serve in violent military operations, and suffer from serious medical conditions can ultimately become stronger. at the opposite side of the spectrum from posttraumatic stress disorder (ptsd), posttraumatic growth (ptg) has been described in healthcare workers (hcws). though an ancient idea, growth from adversity began receiving serious research attention in the 1990s (3). ptg occurs across three domains: self-perception, interpersonal relationships, and life philosophy. growth emerges in five realms: improvement in relating to others, greater personal strength, positive spiritual change, greater appreciation of life, and discovering new possibilities (3) . a systematic review found that 53% of individuals who endure trauma experienced ptg (4), enjoying greater life satisfaction, happiness, psychological, emotional, and even physical wellbeing (5) . predictors of ptg include active coping, self-control, higher education level, hope, social support, and deliberate rumination (making sense of the trauma) (4, 6). moderate to high ptg occurs more commonly in women, younger subjects, and professionals with training (4). personality characteristics that predict ptg include extroversion and openness to experience (7) . individuals experiencing a stressful or traumatic event should adopt a growth mindset, reflect on their experiences, and believe in human resilience. hcws have experienced substantial negative mental health effects during covid-19. though nurses and women may be more susceptible to acute psychological stress (8) (9) (10), they have the most growth potential. a ptg intervention in hcws in china led to pronounced benefits in nurses and women (11) . individuals living in affected geographic regions, and those on the frontline, may be at higher risk of negative emotional effects (12) (13) . interestingly, other studies have demonstrated the opposite: frontline hcws with lower levels of distress (14) (15). while covid-19 has already resulted in negative outcomes for hcws, individuals can still strive for greater appreciation of life, improved self-esteem, and positive approaches to daily responsibilities (16) . after sars 2003, respondents in hong kong reported increased care for family, more focus on mental health, and more time devoted to relaxation (17) . effective practices reframe stressful events to help one find meaning in hardships. in constructing a coherent narrative, one transforms uncontrolled rumination into a "more deliberate, reflective form of thinking" (7) . prior to covid-19, half of physicians experienced emotional fatigue, burnout, depression and suicide (18) . covid-19 has added new physical and psychological pressures that will ripple through the entire healthcare system (19) . according to a recent review of publications on healthcare workers in covid-19, the number one way to reduce stress levels was provision of safeguards to prevent transmission (20) . hcws should only reuse ppe as a last resort, which is associated with higher rate of infection (21) . while telehealth requires resources for planning, implementing, and evaluating, it limits nonessential exposure to infected patients and allows for convenient mental healthcare for providers. despite obvious obstacles, hcws must maintain social connections, which improve health outcomes (22) . hcws should schedule calls and video chats with friends and family, reinforcing community roles. outreach especially benefits those who struggle in isolation. prompt, individualized psychological support is vital. drop-in sessions with mental health professionals showed benefit in one toronto hospital during the sars-cov-1 outbreak (23) . leaders should reduce stigma for those who access these resources, as hcws may not seek professional help due to perceived impact on career opportunities (24) . healthcare administrators could implement wellness initiatives to provide physical and mental growth opportunities. strength conditioning, aerobic work, and high intensity interval training provide direct physiologic long-term health benefits (25) . a nutritious whole foods (unprocessed) diet, with proper intake of micronutrients, becomes even more important during an infectious outbreak. a healthy diet improves energy, brain functioning, mobility, and immunity (26) . hcws have experienced poor sleep during covid-19 (27) . adequate sleep regulates emotions and overall mental health, along with strengthening the immune system (28) (29). mindfulness interventions facilitate self-awareness and presence, with studies repeatedly demonstrating positive effects of meditation on sleep and other mental and physical health outcomes (30) . the covid-19 worldwide pandemic continues to challenge billions of people, with healthcare workers especially vulnerable. maintaining wellness during covid-19 requires solidarity and civic mindedness (31) . rather than downplaying the appropriate stress and fear from covid-19, this discussion of ptg intends to empower hcws. we must actively reflect, utilize coping skills, and approach our lives with positive mindsets. we can educate patients on ptg as we help them navigate the fear and tangible damage from the pandemic. we can embrace the potential enhancement stress can have on overall health, harnessing opportunities to learn from our experiences and achieving ptg (32) . epidemiological and clinical aspects of covid-19; a narrative review covid-19: emergency medicine physician empowered to shape perspectives on this public health crisis the posttraumatic growth inventory: measuring the positive legacy of trauma the prevalence of moderateto-high posttraumatic growth: a systematic review and meta-analysis vicarious posttraumatic growth: a systematic literature review shared and unique predictors of post-traumatic growth and distress prescribing posttraumatic growth psychological impact and coping strategies of frontline medical staff in hunan between factors associated with mental health outcomes among health care workers exposed to coronavirus disease the psychological well-being of physicians during covid-19 outbreak in oman effect of positive psychological intervention on posttraumatic growth among primary healthcare workers in china: a preliminary prospective study differences between health workers and general population in risk perception, behaviors, and psychological distress related to covid-19 spread in italy psychological impact of the coronavirus disease 2019 (covid-19) outbreak on healthcare workers in china. medrxiv vicarious traumatization in the general public, members, and non-members of medical teams aiding in covid-19 control a comparison of burnout frequency among oncology physicians and nurses working on the front lines and usual wards during the covid-19 epidemic in wuhan psychological resilience and post-traumatic growth in disaster-exposed organisations: overview of the literature positive mental health-related impacts of the sars epidemic on the general public in hong kong and their associations with other negative impacts preserving mental health and resilience in frontline healthcare workers during covid-19. the american journal of emergency medicine protecting our healthcare workers during the covid-19 pandemic. the american journal of emergency medicine mental health problems faced by healthcare workers due to the covid-19 pandemic-a review risk of covid-19 among frontline healthcare workers and the general community: a prospective cohort study advancing social connection as a public health priority in the united states mental health care for medical staff and affiliated healthcare workers during the covid-19 pandemic clinician wellness during the covid-19 pandemic: extraordinary times and unusual challenges for the allergist/immunologist can exercise affect immune function to increase susceptibility to infection? a review of micronutrients and the immune system-working in harmony to reduce the risk of infection generalized anxiety disorder, depressive symptoms and sleep quality during covid-19 outbreak in china: a web-based cross-sectional survey the sleep-immune crosstalk in health and disease sleep and emotional processing mindfulness interventions covid-19: doctors must take control of their wellbeing rethinking stress: the role of mindsets in determining the stress response funding none key: cord-286977-330p60oh authors: barcala-furelos, roberto; szpilman, david; abelairas-gómez, cristian; calvete, alejandra alonso; graña, maría domínguez; martínez-isasi, santiago; palacios-aguilar, josé; rodríguez-núñez, antonio title: plastic blanket drowning kit: a protection barrier to immediate resuscitation at the beach in the covid-19 era. a pilot study. date: 2020-09-16 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.101 sha: doc_id: 286977 cord_uid: 330p60oh objective: introducing a new, simple and inexpensive portable equipment for lifeguards, consisting of a pre-assembled full-size plastic blanket with a mask and hepa filter, which could offer significant time-saving advantages to reduce covid-19 risk transmission in the first few minutes of cpr after water rescue, avoiding the negative impact of delayed ventilation. method: a pilot study was carried out to determine the feasibility of the pre-assembled kit of face-mask and hepa filter adapted on a pre-set plastic-blanket. the first step consisted of washing hands, putting on safety glasses and gloves as the first personal protection equipment (ppe) and then covering the victim with an assembled plastic blanket. the second step consisted of 10 min of cardiopulmonary resuscitation (cpr) with ppe and plastic blanket, following the technical recommendations for ventilation during covid-19. results: ten rescuers took part in the pilot study. the average time to wear ppe and place the pre-assembly kit on the victim was 82 s [ic 58–105]. after 10 min the quality of the resuscitation (qcpr) was 91% [87–94]. quality chest compressions (cc) were 22% better than ventilations (v). most of the rescuers (60%) thought that placing the plastic blanket on the victim on the beach was somewhat simple or very simple. conclusions: resuscitation techniques in covid-19 era at the beach have added complexities for the correct use of ppe. plastic blanket plus basic ventilations equipment resource could be a new alternative to be considered for lifeguards to keep ventilation on use while reducing risk transmission. with the emergence of covid-19 [1] disease, there has been a drastic change in the way emergency teams deal with out-of-hospital cardiac arrest and other emergencies. new recommendations for basic life support (bls) from the european resuscitation council during the covid-19 era (erc-covid), [2] propose the use of protective personal equipment (ppe), which significantly delays the starting of chest compressions (cc) and ventilations (v) or do not recommend ventilation at all. drowning is a critical time-dependent circumstance in which cardiac arrest is of an asphyxia origin, so ventilations are essential to revert systemic hypoxia [3] and achieve return of spontaneous circulation. ensuring consistent, correct use of ppe is challenging. it requires training and additional time for donning. [4] when cardiac arrest happens in aquatic environments and lifeguards have to put on and doffing ppe: certain maneuvers are initiated just after the rescue, in which instance both the victim and the lifeguards are wet; and environmental conditions such as hypothermia or hyperthermia difficult its use. additionally, considering that drowning kills 320,000 people worldwide every year, most of whom are in low to medium income countries (lmics), [5] it seems unrealistic to assume that ppe will be available in most of settings. we developed a simple, cost-effective and portable barrier kit to be used in case of drowning cpr. the primary aim of the study was to test the feasibility of this cpr kit designed for the covid pandemic. the ppe kit consists of a pre-assembled full-size transparent plastic blanket with an adaptation to a ventilation face mask with a high efficiency particulate air (hepa) filter.  standard face mask for medical use ambu® mark iv adult size (ballerup,  hepa filter able to adapted to the face mask.  adult size bag with oxygen reservoir. (fig. 1) to optimize the time to deployment, the stored lifeguard backpack kit should be ready to use. it is quite easy to prepare a small opening in the drape. this opening will allow the patient and bvm on the inside of the drape to be connected to the hepa filter, oxygen bag, and rescuer on the outside of the drape. we placed this opening 50 cm from the superior border of the drape. the fixation is be secured by placing a waterproof tape around the connection. the full kit must be placed on the unconscious drowning victim without signs of life in 5 simple steps lasting just one minute, allowing immediate full cpr. -simple‖ and only two participants (20%) considered this process as -difficult‖ or -very difficult‖ (fig.4) . the aim of this report was to show a simple and low cost method, which can help lifeguards at the beach in various ways: as an extra protection attached to ppe, as initial protection when they are wet and cannot wear quickly or correctly ppe (gloves, glasses and plastic coat), in case they decide to provide cpr with a bag-valve mask with hepa filter, or also in lmics that do not have ppe (gloves, glasses and plastic coat), in case they decide to provide cpr with a bag-valve mask with hepa filter. in the covid-19 pandemic the risk of transmission during medical attendance is high. this occurs in techniques or procedures that generate aerosols, such as intubation [7] or any invasive or non-invasive ventilation technique, including the use of bag-valve mask. [8, 9] chan et al showed, how the use of bag-valve mask even with hepa filter, does not prevent 100% air leakage, and how this air leak could reach the rescuer performing cc. [8] . for this reason the use of plastic drapes/patient covering, begins to be explored, to add extra protection during airway interventions[7,10], protecting the laryngoscopist during airway interventions [11] , or covering the patient during prehospital cardiopulmonary resuscitation. [12] these studies and our previous experience in lifesaving have inspired the authors to bring it to an environment with a higher more uncertainty and less control, like a beach. an inadequate lifeguard evaluationvictim is not in cardio-pulmonary arrestmay pose a theoretical limitation if victim is fully covered by interfering with the victim spontaneous breathing. this implies an extra lifeguard training to detect signs of life on the victim and be able to quickly remove the plastic cover. in other circumstances, rescuers may need to remove the blanket: usufoam is generated in drownings of all severity [3] , so the face mask may have to be removed for cleaning up and this may pose a difficulty while using the plastic blanket; foam and water may be need to be aspirated; automatic external defibrillation (aed) may be need as part of bls or the patient may need to be ecg monitored at some point. in addition, some authors have warned of possible risks, such as the permanence of aerosols under the plastic, with the risk of dispersion upon removal [9] . matava et al has suggested the careful removal of the drape plastic to avoid the dispersion of j o u r n a l p r e -p r o o f aerosols. [7] an alternative to aerosol control could include a suction circuit under the drape, [13] but this is not possible in an emergency on the beach. we suggest, in case of use, remove it in an upwind direction, using the plastic as a shield between the patient and the lifeguards. the sea breeze would likely disperse the aerosols in the opposite direction of the lifeguard situation. transport and easy use: the plastic blanket with the hepa filter and mask can be folded and carried in an airtight bag, inside the lifeguard's backpack (rescue bag) along with other rescue material including ppe for cpr. the bag-valve mask should now be a permanent tool for the lifeguard, just like the fins, rescue tube or rescue buoy. suitable for environmental conditions: wind, extreme heat, wet and/or hypothermia after rescue it is a handicap for a correct use/wear ppe, but not for use a blanket plastic. quality cpr maneuvers are possible (at least in this pilot study). both v and cc exceeded an average of 70%, an arbitrary value attributed to quality cpr. [14] an important fact is its low cost. plastic blanket is cheap (less than € 1), which can give access to rescuers without resources or without training in ppe use who want to have extra protection. the need to use ppe during resuscitation of the drowning patient during the covid pandemic has added difficulty to the resuscitation techniques on the beach. plastic blanket could be an alternative to consider for lifeguards when the environment, training or resources require infection transmission protection. the method described here is not intended to replace materials specifically designed for virus transmission prevention. the results of this proposal must be interpreted with the limitations of an experimental model without tests in real patients. we encourage research groups with more resources and emergency medical/lifeguards teams with real experiences using blanket-plastic to report their outcomes. none of the authors has a conflict of interest. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. none of j o u r n a l p r e -p r o o f naming the coronavirus disease (covid-2019) and the virus that causes it european resuscitation council covid-19 guidelines executive summary cognitive load and performance of health care professionals in donning and doffing ppe before and after a simulation-based educational intervention and its implications during the covid-19 pandemic for biosafety world health organization. violence and injury prevention-drowning. world health organization european resuscitation council guidelines for resuscitation 2015: section 4. cardiac arrest in special circumstances mask ventilation and dispersion of exhaled air possible sars coronavirus transmission during cardiopulmonary resuscitation tracheostomy during covid-19 pandemic-novel approach barrier system for airway management of covid-19 patients use of drape/patient covering during potentially aerosolizing procedures clear plastic drapes for aerosol-generating medical procedures in covid-19 patients: questions still remain abc of resuscitation journal pre-proof the authors manufactures medical devices. all authors work for government institutions (hospitals and universities) or non-profit organizations. plastic blanket drowning kit: a protection barrier to immediate resuscitation at the beach in the covid-19 era. a pilot study. key: cord-344154-j5jjl0ok authors: kandil, manar; jaber, sabrin; desai, dharati; cruz, stephany nunez; lomotan, nadine; ahmad, uzma; cirone, michael; burkins, jaxson; mcdowell, marc title: magraine: magnesium compared to conventional therapy for treatment of migraines date: 2020-09-14 journal: am j emerg med doi: 10.1016/j.ajem.2020.09.033 sha: doc_id: 344154 cord_uid: j5jjl0ok due to the healthcare burden associated with migraines, prompt and effective treatment is vital to improve patient outcomes and ed workflow. this was a prospective, randomized, double-blind trial. adults who presented to the ed with a diagnosis of migraine from august of 2019 to march of 2020 were included. pregnant patients, or with renal impairment were excluded. patients were randomized to receive intravenous magnesium, prochlorperazine, or metoclopramide. the primary outcome was change in pain from baseline on a numeric rating scale (nrs) evaluated at 30 min after initiation of infusion of study drug. secondary outcomes included nrs at 60 and 120 min, ed length of stay, necessity for rescue analgesia, and adverse effects. a total of 157 patients were analyzed in this study. sixty-one patients received magnesium, 52 received prochlorperazine, and 44 received metoclopramide. most patients were white females, and the median age was 36 years. hypertension and migraines were the most common comorbidities, with a third of the patients reporting an aura. there was a median decrease in nrs at 30 min of three points across all three treatment arms. the median decrease in nrs (iqr) at 60 min was −4 (2–6) in the magnesium group, −3 (2–5) in the metoclopramide group, and − 4.5 (2–7) in the prochlorperazine group (p = 0.27). there were no statistically significant differences in ed length of stay, rescue analgesia, or adverse effects. reported adverse effects were dizziness, anxiety, and akathisia. no significant difference was observed in nrs at 30 min between magnesium, metoclopramide and prochlorperazine. a migraine is a chronic neurologic disease characterized by attacks of throbbing, often unilateral headache associated with photophobia, phonophobia, nausea, vomiting, and cutaneous allodynia. it is the second most disabling neurologic condition in the united states, resulting in a $27 billion cost due to loss of productivity. [1] [2] it is estimated that there are over 1.2 million visits to emergency departments (ed) in the united states are due to migraines. 3 migraine, previously believed to be a vascular disorder, is caused by inflammation due to vasodilation in the meninges secondary to the release of vasoactive neuropeptides by stimulation of the trigeminal nerve. 4 this inflammation can result in symptoms such as headache, nausea, vomiting, dizziness, photophobia and phonophobia. despite migraine being a common disorder, there has yet to be a cure. several classes of medications have been studied for the treatment of migraine. recently, conventional therapy has shifted to the use of anti-dopaminergics which include prochlorperazine, metoclopramide and haloperidol, nonsteroidal anti-inflammatory drugs (nsaids) such as ibuprofen and naproxen, and serotonin receptor agonists, such as sumatriptan. 5 although intravenous (iv) opioids have historically been the most common treatment for migraines, their use has fallen out of favor due to their association with increased recurrence of headaches and ed visits, abuse potential, and most recently severe iv opiate shortage. 6 alternative treatments include ketamine, propofol, dihydroergotamine, and magnesium. 5 j o u r n a l p r e -p r o o f magnesium is an intracellular cation that has been associated with both the function of serotonin and regulation of vascular tone, which are both mechanisms that implicate its role in the treatment of migraine. 7 intravenous magnesium sulfate has been studied as a treatment for migraine and has been compared to placebo, metoclopramide and prochlorperazine in previous studies. [7] [8] [9] [10] [11] [12] these studies have demonstrated that magnesium is well-tolerated with a good safety profile and may be efficacious in the treatment of migraine. metoclopramide, prochlorperazine, and magnesium have been recommended in clinical practice guidelines and have commonly been used for treatment of migraine in the ed. [13] [14] however, no trial has evaluated all three of these drugs within the same population. the purpose of our study was to compare the relative efficacy of magnesium, metoclopramide, and prochlorperazine for the treatment of headache and migraine in the ed. this study was a single-center, prospective, double-blinded, randomized-controlled, three-armed trial comparing magnesium, metoclopramide, and prochlorperazine for the treatment of migraine. this trial was conducted in a large, level 1 trauma, tertiary-care medical center ed near chicago, illinois from august of 2019 through march of 2020. patients greater than or equal to 18 years of age presenting to the ed with a chief complaint of migraine or headache while an ed pharmacist was present were eligible for inclusion in this study. migraine diagnosis was determined by an ed physician after thorough j o u r n a l p r e -p r o o f journal pre-proof examination to rule out migraine mimics or headache conditions where traditional migraine therapy would be deemed inappropriate. patients were required to have the ability to provide informed consent. exclusion criteria included pregnancy, a stated history of renal impairment, allergy or sensitivity to any of the study drugs, or receipt of any of the study drugs prior to enrollment. following assessment for study eligibility, patients were consented by the ed pharmacist. patients were randomized to receive one of three study drugs (magnesium sulfate 2gm, metoclopramide 10mg, or prochlorperazine 10mg) via computer randomization. study drug randomization and preparation was the responsibility of the iv room pharmacist who was not part of the study. the ed pharmacists, physicians, and nurses participating in administration of the medications were blinded to which drug was selected. magnesium sulfate 2gm/50ml d5w, prochlorperazine 10mg/50ml d5w, or metoclopramide 10mg/50ml d5w was then administered as an iv infusion over 20 minutes. the primary outcome of this study was change in pain from baseline to 30 minutes after initiation of infusion. pain was assessed by the ed pharmacist using the 11-point numeric rating scale (nrs) and recorded on a data collection tool. nrs is a validated tool commonly used to measure different types of pain. 15 secondary endpoints included change in pain score from baseline to 60 minutes and 120 minutes after initiation of infusion (as defined on a 11-point nrs), ed length of stay, and j o u r n a l p r e -p r o o f journal pre-proof necessity for rescue analgesia at any time following the study drug administration. safety endpoints included monitoring for common adverse effects related to the study drugsprimarily hypotension, flushing, akathisia, dystonia, nausea, vomiting, dizziness, drowsiness, or other self-reported adverse effects [16] [17] [18] . patient baseline characteristics were also collected, which included patient-reported past medical history and analgesic use prior to presenting to the ed. a sample size of 264 subjects (88 subjects per treatment arm) was calculated to detect a difference of 1.4 points in the nrs between groups to achieve a power of 80%. 19 statistical significance was defined a priori as p<0.05, and normality was assessed using the shapiro-wilk test. descriptive statistics were used for nominal data, while ordinal and categorical data were evaluated using mann-whitney u and pearson's χ 2 , respectively. between-group comparisons were made using one-way anova and kruskal-wallis, as appropriate for all continuous data. a post hoc non-inferiority analysis of the primary endpoint was conducted using welch's t-test with a non-inferiority margin of 1.4. 20 data analysis was performed through sas software for windows (version 9.4). 21 during the study period, a total of 163 patients were consented for enrollment ( figure 1 ). due to covid-19, enrollment was terminated prematurely and only 157 patients were included in the final data analysis. no significant differences between baseline demographics were observed (table 1). the majority of the patients were white, female, and the median age approximately 50% of patients reported taking medications to abort their migraine prior to presenting to the ed. the most common medications taken prior to presentation to the ed were acetaminophen and nsaids (appendix table a1). upon admission to the ed, more than two-thirds of the patients received medications prior to receiving the study medication (table 2). over 70% of patients received a dose of iv diphenhydramine prior to the study medication to prevent potential adverse effects such as akathisias. other concomitant therapies included acetaminophen, iv nsaids, dexamethasone, and ondansetron (appendix table a2). the median (iqr) baseline pain score for patients in the magnesium group was 8 (7-10), 8 (7-9.5) in the metoclopramide group, and 9 (7-10) in the prochlorperazine group. although the baseline pain scores were slightly higher in the prochlorperazine group, this was not statistically significant (p= 0.52). figure 2 highlights the median pain scores for patients at baseline, 30, 60, and 120 minutes after the study drug infusion. based on the results of the mann-whitney u analysis, the changes in pain scores from baseline to 30 minutes within each group were statistically significant (p< 0.01). however, the kruskal-wallis one-way analysis for variance demonstrated that differences in median pain scores between each treatment arm were not statistically significant (table 2). while prochlorperazine did appear to have a greater effect on pain reduction at one hour, this was not statistically significant (p= 0.27). it is worth noting that the sample sizes of each group decreased as time progressed, presumably due to j o u r n a l p r e -p r o o f journal pre-proof patients being discharged prior to the full duration of data collection. interestingly, there was no difference in ed length of stay between groups (table 4). more patients in the magnesium group required rescue analgesia, defined as the necessity for additional medications following the administration of the study drug. approximately one third of patients received a dose of rescue analgesia between 30 to 120 minutes after receiving the study drug (table 3). the most commonly administered rescue analgesics were iv nsaids, anti-dopaminergic agents, and acetaminophen. other agents included opiates, ondansetron, and the combination of acetaminophen, butalbital, and aspirin (appendix table a3). finally, adverse events were reported in 5% of patients in the magnesium group, 4.5% in the metoclopramide group, and 11.5% in the prochlorperazine group (p=0.51). the most commonly reported adverse effects were dizziness, akathisias, and anxiety. the akathisias occurred in the prochlorperazine group, requiring treatment with diphenhydramine. no statistically significant differences in change in pain scores were found between all three treatment arms; however, a post hoc noninferiority analysis revealed that when compared to prochlorperazine and metoclopramide, iv magnesium was non-inferior ( figure 3) . the difference between the mean pain score in the magnesium group compared to the prochlorperazine group was 0.08, which was well below the non-inferiority margin (p<0.01). similarly, the difference between the mean pain score in the magnesium group compared to the metoclopramide group was 0.18-also below the noninferiority margin (p<0.01). j o u r n a l p r e -p r o o f the results of the magraine study demonstrated that iv magnesium sulfate, metoclopramide, and prochlorperazine were effective in decreasing pain scores for migraines at 30, 60, and 120 minutes, however one agent was not superior to the rest. although prochlorperazine trended towards a greater decrease in pain scores at 60 minutes, this potential benefit may be offset by the increased adverse effects, mainly akathisias. our results suggest that magnesium may have had a faster onset, which is consistent with the results of shahrami and colleagues. 12 however, shahrami compared magnesium sulfate to concomitant administration of metoclopramide and dexamethasone, and therefore the dexamethasone may have contributed to the delayed effects of metoclopramide. corbo and colleagues reported that combination therapy of magnesium sulfate with metoclopramide resulted in decreased efficacy of metoclopramide, however the results of our non-inferiority analysis demonstrated that magnesium sulfate was non-inferior to metoclopramide. 8 limitations of the study include the unexpected premature termination of recruitment, which ultimately lead to unequal treatment arms and the study being underpowered. this makes it difficult to draw conclusions with regards to whether one agent fared better for migraine abortion. furthermore, there was no uniform protocol for time to initiation of medications in the ed prior to study drug administration or for rescue therapy. this ultimately could have confounded the results of this study since it is unknown if pain relief was related to the administration of the study drug versus adjunctive therapies. additionally, the choice of adjunctive therapies was at the physician's discretion. approximately one third of patients received additional therapies prior to 120 minutes, which may have also confounded migraine relief. finally, although there was no difference in ed length of stay between groups, the length j o u r n a l p r e -p r o o f journal pre-proof of stay may have varied due to the timing of presentation to the ed, and prioritization for high acuity patients. there was no statistically significant difference in change in median pain scores between iv magnesium, metoclopramide, and prochloperazine. however, iv magnesium was not inferior to prochlorperazine or metoclopramide at 30 minutes when treating headaches and migraines in the ed-despite patients requiring greater rescue analgesia. although prochlorperazine may be more effective at controlling pain at one hour, it may also result in greater adverse effects. iv magnesium may be used as an adjunctive agent for the treatment of migraines, or may serve as a safe alternative when agents such as prochloperazine or metoclopramide are not appropriate. quickstats: percentage of adults aged ≥18 years who reported having a severe headache or migraine in the past 3 months, by sex and age group -national health interview survey, united states global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the global burden of disease study current management of migraine in us emergency departments: an analysis of the national hospital ambulatory medical care survey the pathophysiology of migraine: implications for clinical management managing migraine convincing the skeptic. how to fix emergency department headache management randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache a prospective study of i.v. magnesium and i.v. prochlorperazine in the treatment of headaches magraine: magnesium compared to conventional therapy for treatment of migraines efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. a randomized, double-blind, placebo-controlled study a randomized prospective placebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the emergency department comparison of therapeutic effects of magnesium sulfate vs. dexamethasone/metoclopramide on alleviating acute migraine headache the acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies the 2012 ahs/aan guidelines for prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines pain assessment magraine: magnesium compared to conventional therapy for treatment of migraines 17 wolters kluwer health practical guide to sample size calculations: non-inferiority and equivalence trials hannah henderson, pharmd candidate; elishka braun, pharmd appendix a: key: cord-339864-rv5zw972 authors: reihani, hamidreza; ghassemi, mateen; mazer-amirshahi, maryann; aljohani, bandar; pourmand, ali title: non-evidenced based treatment: an unintended cause of morbidity and mortality related to covid-19 date: 2020-05-06 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.001 sha: doc_id: 339864 cord_uid: rv5zw972 nan nonevidence-based remedies are spreading across different populations and endangering the lives of individuals, particularly those with low health literacy. for example, given the sacredness of cows in india, some hindus are drinking cow urine to prevent covid-19, a practice backed by government officials [4] . in iran, social media accounts circulated false stories of curing covid-19 by drinking high-proof alcohol, poisoning over 2,000 people due to the inadvertent consumption of methanol with bleach to hide its color [5] . the quick spread of misinformation regarding nonevidence-based treatments for covid-19 may be due to feelings of fear, helplessness, and hope. because there is no definitive treatment for covid-19, people j o u r n a l p r e -p r o o f seek remedies based on their level of knowledge and personal or popular beliefs, which is detrimental to both their own health and the public's health. in the united states, president donald trump suggested the possibility of injecting a disinfectant into patients with sars-cov-2 infection or treating them with ultraviolet rays [6] . these remarks are not only dangerous because disinfectants are poisonous when mishandled, but when these statements are circulated to populations with low health literacy, people may poison themselves from self-administration. of note, even before this statement, there had been a 20% increase in calls to u.s. poison centers related to disinfectants and cleaning products compared to last year [7] . while some of these calls are related to accidental pediatric exposures, others involve inadvertent misuse of the product [7] . there were notable increases in inhalational exposures, as well as exposures to bleach products and alcohol-based sanitizers [7] . even though chloroquine derivates are not approved treatments for covid-19, president trump has tweeted and publicly suggested the therapeutic benefit of the drugs. due to the media attention surrounding chloroquine, an arizona man died after ingesting chloroquine phosphate (an additive to household products meant to treat fish parasites) in an effort to prevent himself from getting infected with coronavirus. [8] . in madagascar, president andry rojoelina launched an herbal coronavirus "cure" produced from the artemisia plant, yet the who stated that the tonic is not evidence-based and is potentially toxic [9] . touting unproven covid-19 treatments will only worsen the current healthcare crisis, as people will certainly experiment with these remedies. as a result, health care systems will become overwhelmed with many critically ill patients, from both covid-19 and those with toxicity from nonevidence-based treatments. there has also been increased media coverage for "alternative" remedies to prevent and treat sars-cov-2 infection. for example, the chinese government encourages the use of herbal j o u r n a l p r e -p r o o f plants to fight the virus including jinhua qinggan capsules, lianhua qinwen capsules, and shufeng jiedu capsules [10] . these herbal formulas contain a combination of many herbs and the exact proprietary mixture is not available, posing a major health risk to patients due to their potential toxicity, contamination, or adulteration [10] . although traditional medicine techniques were widely used during past epidemics such as severe acute respiratory syndrome (sars) and h1n1 influenza, a cochran review found that chinese herbs combined with western medicine did not decrease mortality versus western medicine alone [11] . use of chinese herbal products for treating viruses is not guided by viral pathology, rather herbs are prescribed by herbalists according to chinese diagnostic patterns (inspection, listening, smelling, inquiry, and palpitation) [12, 13] . the implications of medicating with herbal-based formulas is serious and dangerous because there is no scientific evidence suggesting that these alternative remedies can prevent or cure covid-19. there are several adverse effects noted with herbal medications, such as hepatotoxicity, and there have been numerous reports of toxic contaminants, including pesticides and heavy metals [14] . furthermore, although supplementing with vitamins and minerals may improve immune function, there is no evidence to suggest that the use of any supplement will prevent or cure covid-19. similarly, "cures" spread by iranian social media accounts (which include gargling vinegar and rosewater or salt, and drinking concoctions of mint or white willow with saffron, turmeric, and cinnamon) are not evidence-based, though they may have other nutritional benefits [15] . medicating with these herbal formulas or supplements may lead to adverse health effects due to imprecise dosing of the supplement or herb, inherent toxicity of the herb itself, or toxicity of the contaminants in the product, thus complicating the clinical picture. the spread of nonevidence-based covid-19 treatments or cures will undoubtedly worsen the magnitude of the pandemic. as people turn to traditional and nonevidence-based therapeutic options for covid-19 patients a trial of lopinavir-ritonavir in adults hospitalized with severe covid-19 are patients with hypertension and diabetes mellitus at increased risk for covid-19 infection? hindu group offers cow urine in a bid to ward off coronavirus [internet]. reuters iran, false belief a poison fights virus kills hundreds public broadcasting service trump suggests 'injection' of disinfectant to beat coronavirus and 'clean' the lungs nbcuniversal news group cleaning and disinfectant chemical exposures and temporal associations with covid-19 -national poison data system fearing coronavirus, arizona man dies after taking a form of chloroquine used in aquariums cable news network coronavirus: caution urged over madagascar's 'herbal cure china is encouraging herbal remedies to treat covid-19. but scientists warn against it nbcuniversal news group chinese herbs combined with western medicine for severe acute respiratory syndrome (sars) in silico screening of chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus traditional chinese herbal medicine for treating novel coronavirus (covid-19) pneumonia: protocol for a systematic review and meta-analysis toxicities by herbal medicines with emphasis to traditional chinese medicine misinformation and false medical advice spreads in iran risk communication: epi-win world health organization. world health organization key: cord-311353-ozqfsuh8 authors: sun, chun-yang; sun, ya-lei; li, xin-min title: the role of chinese medicine in covid-19 pneumonia: a systematic review and meta-analysis date: 2020-07-08 journal: am j emerg med doi: 10.1016/j.ajem.2020.06.069 sha: doc_id: 311353 cord_uid: ozqfsuh8 introduction: chinese medicine (cm) has been used to treat novel coronavirus 2019 (covid-19) pneumonia in china. this meta-analysis was conducted to evaluate the clinical efficacy and safety of cm in the treatment of covid-19 pneumonia. methods: randomized controlled trials (rcts) involving cm in the treatment of covid-19 pneumonia were identified from cochrane central register of controlled trials, pubmed, embase, chinese national knowledge infrastructure, chinese biomedical database, wanfang database and vip information database. the methodological quality of trials was evaluated with cochrane hanadbook criteria, and the cochrane collaboration's review manager 5.3 software was used for meta-analysis. results: a total of 7 valid studies involving 681 patients were included. the meta-analysis exhibited in comparison to conventional treatment, cm combined with conventional treatment significantly improved clinical efficacy (rr = 1.21, 95% ci [1.08,1.36]), and significantly increased viral nucleic acid negative conversion rate (rr = 1.49, 95% ci [1.13,1.97]). cm also prominently reduced pulmonary inflammation (rr = 1.27, 95% ci [1.12,1.44]), and improved host immune function (wbc, md = 0.92, 95% ci [0.07,1.76]; lym, md = 0.33, 95% ci [0.08,0.57]; lym%, md = 2.90, 95% ci [2.09,3.71]; crp, md = −12.66, 95% ci [−24.40, −0.92]). meanwhile, cm did not increase the incidence of adverse reactions (rr = 1.17, 95% ci [0.39,3.52]). conclusion: according to the allocated data, cm has demonstrated clinical efficacy and safety on covid-19 pneumonia, which need to be confirmed by high quality, multiple-center, large sample randomized controlled trials. novel coronavirus disease 2019 pneumonia is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2), which firstly appeared in wuhan, china [1] [2] . it is highly infectious and spreads through respiratory droplets and contact [3] . it is characterized by acute onset, severe symptoms, such as dyspnea and multi-organ dysfunction [4] . the world health organization listed this pneumonia epidemic of wuhan, china, as a public health emergency of international concern [5] . the world is now facing a pandemic of covid-19, for which no proven specific therapies are available, other than supportive care. on january 20, 2020, national health commission of the people's republic of china announced that covid-19 would be classified as category a infectious disease [6] . at the same time, chinese medicine experts quickly reached a consensus on chinese medicine (cm) therapy. as medical therapy, cm treatment was written in "diagnosis and treatment of pneumonia infected by 2019-ncov (trial implementation 7th edition)" published by national health commission of the people's republic of china [7] . however, compared with conventional treatment, there is no high-level evidence to support the effectiveness of cm treatment. therefore, the meta-analysis method will be used to systematically review the clinical efficacy and safety of cm for covid-19 pneumonia. this analysis is expected to obtain meaningful conclusions and provide a high level of evidence-based medicine evidence. studies meeting the following criteria were included: (1) randomized controlled trials (rcts) using cm (including chinese herbal medicine, chinese patent medicine and chinese medicine injections) to treat covid-19 pneumonia regardless of j o u r n a l p r e -p r o o f meta-analysis. if two or more homogeneous studies are available, we will use aggregated data for meta-analysis. if the data are not available for quantitative analysis, we will report result by qualitative description. for dichotomous outcomes, we calculated the risk ratio (rr), 95% confidence intervals (ci) and p values. for continuous variable, we calculated the mean difference (md), 95% ci and p values. we used the inverse variance method to calculate pooled md values and the mantel-haenszel estimator to calculate rr. studies will be evaluated for heterogeneity using i squared and chi-squared test. if i 2 >50%, or p0.05, the studies will be considered heterogeneous, and the pooling model will choose a random effects model, otherwise fixed effects model will be used. the funnel plot will be used to evaluate publication bias. 716 unique citations were identified from electronic database. after duplicates removed, 697 literature remained. by reading titles and abstracts, 42 articles were downloaded. a total of 42 articles were retrieved for further assessment, among which 35 were further excluded, for the reasons: wrong patient population; self-control; retrospective studies. in total, seven [9] [10] [11] [12] [13] [14] [15] rcts met the inclusion criteria and were subjected to data extraction ( figure 1 ). all studies included involved seven rcts with 681 patients. of the seven rcts, two rcts [9, 13] reported clinical effective rate, seven rcts [9] [10] [11] [12] [13] [14] [15] recorded incidence of adverse reactions, three rcts [10, 11, 14] reported viral nucleic acid negative conversion rate, four rcts [10, [12] [13] [14] recorded remission rate of pulmonary inflammation (chest ct). there were three rcts [9, 13, 14] reported white blood cell count (wbc), three rcts [9, 10, 14] reported lymphocyte count (lym), two rcts [9, 13] reported lymphocyte ratio (lym%), four rcts [9, 10, 12, 14] reported c-reactive proteins, and two rcts [12, 14] reported interleukin-6. the comparison of baseline characteristics showed there were no significant differences in gender, age, or disease duration between the treatment and control groups (p>0.05). the characteristics of the studies are illustrated in table 1 j o u r n a l p r e -p r o o f for the eligible studies, three studies [9, 12, 15] the clinical effective rate was tested in two rcts involved 273 patients. the efficacy criteria were predominantly based on reduction of clinical symptoms and could be divided into three grades: cured, remarkable recovery, unrecovered. the rate calculated by this formula: (number of cured patients+number of remarkable recovery patients)/total number×100% [16] . heterogeneity test results(p=0.39, i 2 =0%) indicated that there were no statistical significant difference between the studies, and the fixed effect model was selected for meta-analysis. as can be observes in figure taking incidence of adverse reactions into consideration (including seven rcts, 681patients), we noted there is high heterogeneity between studies(p=0.03, i 2 =62%). therefore, it was decided to choose the random effect model for meta-analysis. the chest ct findings were typical of findings for covid-19 pneumonia [17, 18] . figure 6 ). the results indicated that, compared with conventional treatment alone, combined therapy with cm can significantly reduce pulmonary inflammation (chest ct). [27] [28] [29] . these immunological markers may be of importance due to their correlation with disease severity in covid-19. there are no specific pharmacological interventions discovered for treatment of covid-19 pneumonia so far. the world health organization recommended that potential antiviral medicines should be developed [30] . however, the development of potential antiviral medicines may take months, even years. in consideration of these limitations, the application of chinese medicine could be promoted. showed that cm has excellent outcomes in the treatment of covid-19, bringing new hope for the control of covid-19 pneumonia [9] [10] [11] [12] [13] [14] [15] . the results of this meta-analysis are encouraging. in terms of clinical effective rate, viral nucleic acid negative conversion rate, remission rate of pulmonary inflammation, and biochemical markers, cm exhibited superior performance. meanwhile, cm has therapeutic safety. as the first meta-analysis evaluating the efficacy and safety of cm for the treatment of covid-19 pneumonia, the wide extent of literature screening and the introduction of statistical analysis methods have ensured the validity of this review, as well as providing a rational conclusion. it is critical for clinicians to accurately determine the severity of a patients condition. at the same time, clinicians follow the theory of chinese medicine, and determine the appropriate prescription to ensure effective treatment. especially, in the absence of chinese herbal medicine, a variety of a review of coronavirus disease-2019 (covid-19) the transmission and diagnosis of 2019 novel coronavirus infection disease (covid-19): a chinese perspective clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan world health organization. who director-general's statement on ihr emergency committee on novel coronavirus national health commission of the people's republic of china. pneumonia infected by covid-19 included in the management of legal infectious diseases updated guidance for trusted systematic reviews: a new edition of the cochrane handbook for systematic reviews of interventions clinical study on 37 case of covid-19 treated with integrated traditional chinese and western medicine multi-center clinical observation of reyanning mixture in treatment of novel coronavirus pneumonia observation on clinical effect of shufeng jiedu capsule combined with arbidol hydrochloride capsule in treatment of covid-19 analysis of the value of shufeng jiedu capsules combined with abidol in the treatment of mild novel coronavirus pneumonia treatment of covid-19 by pneumonia no.1 prescription and pneumonia no.2 prescription clinical observation of jinhua qinggan granule in treating pneumonia infected by novel coronavirus guiding principles for clinical research of new chinese medicines. 1 th ed. beijing, china: china medical science and technology press use of chest ct in combination with negative rt-pcr assay for the 2019 novel coronavirus but high clinical suspicion correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases a novel coronavirus from patients with pneumonia in china genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding world health organization chest ct for typical 2019-ncov pneumonia: relationship to negative rt-pcr testing a rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-ncov) infected pneumonia (standard version) clinical, laboratory and imaging features of covid-19: a systematic review and meta-analysis characteristics of peripheral blood leukocyte differential counts in patients with covid-19 clinical and immunologic features in severe and moderate coronavirus disease anti covid-19 drugs: need for more clinical evidence and global action key: cord-298640-zwg8ueyb authors: smereka, jacek; szarpak, lukasz title: the use of personal protective equipment in the covid-19 pandemic era date: 2020-04-15 journal: am j emerg med doi: 10.1016/j.ajem.2020.04.028 sha: doc_id: 298640 cord_uid: zwg8ueyb nan the use of personal protective equipment in the covid-19 pandemic era american journal of emergency medicine xxx (xxxx) xxx yajem-158899; no of pages 2 in the times of sars-cov-2 pandemic, particular attention should be paid to personal protective equipment (ppe). medical personnel protection is of particular importance because of the risk of infecting other members of medical teams, including not only physicians, nurses or paramedics, but also other support personnel necessary to maintain the continuity of care for patients [1, 2] . medical personnel protection is a priority as in their case, infection or even the need for quarantine may pose a real threat to patients. the weaknesses of health care systems in many countries are now particularly highlighted. even the highly developed countries with the highest level of health care systems cannot cope with a sudden increase in the number of patients in need of treatment, including, primarily, intensive care with endotracheal intubation and mechanical ventilation [3] . the need to limit therapy to survivors constitutes an enormous psychological burden and moral and ethical challenge; it also triggers a number of negative phenomena among the affected families and the medical personnel themselves [1, 4] . the current pandemic is reducing medical resources and requires ppe adaptation to the circumstances and to the scale of the threat to medical personnel [5] . one should remember that it is the most important to follow the general recommendations on hand disinfection and the sequence of procedures when putting on and taking off ppe [6] . it is essential to use masks with a filter, but also goggles and visors to protect the face, as well as double or triple gloves (fig. 1) . sterile surgical gloves are particularly useful as they are longer. the optimal solution is to fully protect the entire body surface, isolate it from the environment, and breathe in air from a portable source, but this is not necessary in the case of sars-cov-2 [7] . at present, it is recommended to apply various types of equipment, including, in particular, partial protection of the environment through the use of surgical masks or ordinary face masks by persons with confirmed or potential sars-cov-2 infection; this may reduce the risk of infecting people in the environment, including medical personnel [3, 7] . at present, performing a number of procedures in emergency medicine is associated with additional problems and risks for medical personnel. emergency physicians, anesthesiologists and intensive care specialists, as well as the relevant scientific societies issue recommendations concerning endotracheal intubation or other procedures dangerous for the medical personnel [1, 2] . it should be remembered that endotracheal intubation by using direct laryngoscopy without adequate protection presents a high risk of sars-cov-2 infection. the proposed modifications of endotracheal intubation include special preparation of the equipment and medical personnel, using a special protective box, foils applied to the upper half of the patient's body, and the use of indirect laryngoscopy methods, including video laryngoscopy and rapid sequence intubation [8, 9] . in this context, it should be emphasized that attempts of prehospital endotracheal intubation by inexperienced personnel constitute a challenge, and supraglottic methods should be kept in mind. if intravenous access cannot be established or is technically difficult, it is still possible to establish intraosseous access. performing several procedures in protective clothing is technically difficult and exhausting, which is especially true for cpr. certain intrahospital procedures must be modified, for example, cardiopulmonary resuscitation in a patient with ards in a prone position and electrical defibrillation. the covid-19 pandemic poses a huge challenge for emergency teams, as well as physicians in emergency departments. the need for additional protection of the patient and medical personnel may result in a significant delay in the arrival of the emergency team, patient transport, and provision of intended medical care. during any pandemic, people still suffer from various diseases and injuries that require treatment. the need to regroup medical forces and resources should not increase morbidity or mortality from diseases other than covid-19. practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-ncov) patients covid 19 a challenge for emergency medicine and every health care professional challenges to the system of reserve medical supplies for public health emergencies: reflections on the outbreak of the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) epidemic in china modern medicine in covid-19 era covid-19: towards controlling of a pandemic. lancet covid-19, a worldwide public health emergency world health organization declares global emergency: a review of the 2019 novel coronavirus (covid-19) your covid-19 intubation kit the italian coronavirus disease 2019 outbreak: recommendations from clinical practice key: cord-268840-m3fp9q3p authors: sahu, ankit kumar; mathew, roshan; bhoi, sanjeev; sinha, tej prakash; nayer, jamshed; aggarwal, praveen title: lung sonographic findings in covid-19 patients date: 2020-09-04 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.080 sha: doc_id: 268840 cord_uid: m3fp9q3p objective: the objective of this study was to describe the lung sonographic findings of covid-19 patients prospectively and investigate its association with disease severity. methods: this study was conducted in an emergency department and included consecutively enrolled laboratory confirmed covid-19 patients. lung sonography findings were described in all the included patients and analysed with respect to the clinical severity of the patients. results: 106 patients were included in the study. common sonographic findings in covid-19 patients were pleural line irregularity or shredding (70% of patients), followed by b – profile (59%), pleural line thickening (33%), occasional b – lines (26%), sub-pleural consolidations (35%), deep consolidations (6%), spared areas (13%), confluent b – lines or waterfall sign (14%) and pleural effusion (9%). these findings tended to be present more bilaterally and in lower lung zones. sonographic characteristics like bilateral lung involvement, b – profile, spared areas and confluent b – lines or waterfall sign were significantly associated (p < 0.01) with clinical severity (more frequent with increasing disease severity). conclusion: the lung sonographic findings of covid-19 were found more bilaterally and in lower lung zones, and specific findings like b – profile, pleural thickening, spared areas and confluent b – lines or waterfall sign were associated with severe covid-19. lung ultrasound (lus) is a powerful bedside tool which helps in clinical decision making in various conditions. [1] in the covid-19 pandemic, lus has shown its major utility in triaging and management of patient due to its point of care use, safety and repeatability. [2] the clinical spectrum of covid-19 patients range from asymptomatic to critical illness, which can include severe acute respiratory distress (ards) requiring ventilatory support [3] [4] [5] [6] . lus can help in early detection, triaging the patients and monitoring the progression the disease [7, 8] . various studies have documented the different lung sonographic findings of covid19 , which include pleural line abnormalities; focal, multifocal, confluent b-lines and varied patterns of consolidation [7, 9] . lus is highly sensitive and specific in detecting findings of pneumonia and are useful alternative to chest radiograph and computed tomography [10] . switching to ultrasound for clinical evaluation will reduce physicians need to use the stethoscope as it is difficult to use it while wearing personal protective equipment(ppe) [11] . ultrasound also gives an advantage of limiting the movement of the patient and thus, preventing unnecessary exposure to healthcare workers and other patients. in our emergency department (ed), we have incorporated lus in the initial screening of patients with severe acute respiratory infection. through this study we investigated the various lus findings of covid-19 patients. this study was conducted in the ed of a tertiary care hospital of india having an emergency medicine residency program, with an annual ed volume of nearly 200,000 patients. the study period was from april 18 to may 30, 2020. all patients (14 year or older) with suspected covid-19 were screened prospectively and recruited consecutively. 'suspect case' was defined as the patients with acute respiratory infection i.e. "fever with at least one of the respiratory signs and symptoms like cough or dyspnoea", after exclusion of any alternative diagnosis, with a history of travel to or residence in country or territory which had reported local transmission of covid-19 during last 2 weeks prior to symptoms, requiring hospitalisation [12, 13] . all patients with respiratory illness and a history of contact (providing health care, sharing same environment, traveling together, etc) with a confirmed covid-19 case in last 2 weeks were also called as 'suspect case' [12, 13] . among them, only 'laboratory confirmed' cases (positive nucleic acid of sars-cov-2 detected by rt-pcr) were included in the study, and their clinical and lung sonographic findings were documented in a pre-designed data collection form. [12] confirmed covid-19 patients were categorised by the treating physician (also performed the ultrasound) according to their severity of illness according to chinese cdc definitions (mild disease: patients with respiratory tract infection, not fulfilling criteria for severe and critical disease, severe disease: any of the following signs or symptoms like shortness of breath, respiratory rate > 30/min or oxygen saturation < 93%, and critical disease: patients requiring intensive care for organ failure or invasive ventilation) [11] . approval from the institute ethics committee was taken prior to the initiation of this study (iec-262/17.04.2020). the sonosite micromaxx ultrasound device (bothell, wa 98021, usa), equipped with curvilinear (3 -5 mhz) and linear (6 -13 mhz) transducers, was used. all patients underwent lus scanning in a standardized way. eight lung zones (4 in each hemithorax) were scanned (lung zone #1 -extended from 2 nd rib to 6 th rib in the mid-clavicular line, lung zone #2 -extended from 6 th rib to 10 th rib in the mid-clavicular line, lung zone #3 -extended from 4 th rib to 12 th rib in the mid-axillary line and lung zone #4 -extended from 4 th rib to 12 th rib in the scapular line). the images of different areas of lungs were examined one after another. the above examinations were performed by emergency physicians with formal training (didactic lectures with hands-on training by em faculty) in 'emergency ultrasonography' [15] and minimum of 2-years' experience in performing point-of-care ultrasound (pocus). separate ultrasound machines and probes were used for imaging to prevent cross infection. probe covers and low-level disinfectants were utilised for infection control. [16] lung sonographic findings detailed study participants characteristics (demographic data, clinical symptoms, vitals and comorbidities) are depicted in table 1. patients were of older age (median age -47, iqr: 39 -57) and majority of them were male (62%). common presenting symptoms were shortness of breath (72%), cough (61%) and fever (59%). the median duration of shortness of breath was 3 days (iqr: 3 -6) and fever was 4 days (iqr: 3 -6). more than two-thirds of patients had comorbid illnesses (63%). at presentation, a total of 29 patients had 'mild' disease, 41 patients had 'severe' disease, and 36 patients had 'critical' disease category. details of lung sonographic findings are depicted in table spared areas and confluent b -lines (figure -2c) were found in 13% and 14% of the study population respectively. the pleural effusion was seen in 10 patients (figure -2d) . these findings tend to be present more bilaterally and in lower lung zones (lung zone -3 and 4), as shown in table all the sonographic findings were analysed according the patient's presenting disease severity (table -3 ). all these findings were more common in 'severe' and 'critically' ill patients, than that of 'mild' ill patients, except occasional b -lines (common in mild disease). overall comparison of prevalence of bilateral lung involvement was not significant across the disease severity categories (p = 0.095), but pairwise comparison showed more bilateral lung involvement in severe/critical disease, as compared to that of mild disease (p = 0.034). b -profile, pleural thickening, spared areas and confluent b -lines or waterfall sign were significantly correlated with clinical severity (p<0.05). the utility of lus in diagnosis and management of patients with respiratory illness is well documented [1, 19] . during this covid-19 pandemic, our emergency department incorporated the ultrasound in screening patients of acute respiratory illness at the separate triage desk for covid-19 'suspects' [20, 21] . use of pocus in clinical evaluation of the patients has many advantages. first, it acts as a visual stethoscope aiding the ep with real time images of the lung, improving their decision power. second, it removes the need of using an actual stethoscope for auscultation, which becomes difficult to use with the personal protective equipment. third, this helped us in preventing the movement of patients to a radiology suite, reducing unnecessary exposure to healthcare workers. studies have shown the lus findings in covid-19 correlate strongly with ct findings, so replacing lus with ct scan reduces radiation exposures to the patient [22, 23] . our study demonstrated covid-19 lus findings like pleural line abnormalities (pleural line irregularity or shredding and thickening), b-profile and sub pleural consolidations. in two case series of 20 patients each with confirmed covid-19 by peng et al [9] and huang et al [24] , demonstrated similar lus findings which were consistent with ct findings. pleural line abnormalities were the most common finding seen in our study. sub pleural consolidations were more frequently seen when compared to deeper consolidation. this correlated with the more peripheral involvement of the lung in the disease process. [17] pleural effusion was rarely seen in patients. out of the 106 patients included in our study, 36 had 'critical' illness who presented to emergency in acute respiratory distress. acute respiratory distress syndrome (ards) is characterized by heterogeneous b lines, with or without lung sliding and subpleural j o u r n a l p r e -p r o o f consolidations [25] . early detection of these finding on a lung ultrasound can help predict the disease severity of the patient. our study is consistent with smith et al [17] that also demonstrated these findings among patients with increased clinical severity. patients with severe and critical disease had more bilateral lung involvement; there were 'confluent blines' known as the waterfall sign with spared areas, which is more specific for a critical illness. as the disease progresses, there is more interstitial thickening and inflammation, leading to an increase in pleural line irregularities and b-line artifacts seen on lus. [9] it is important to recognize the different characteristic of lus in covid-19 patient in different stages of this disease. this will help in initial triage and decision making for such patients. there are certain limitations of using lus; firstly, it is operator-dependent and requires training for image acquisition and interpretation. second; an extensive examination of lung using ultrasound can take at least 10 minutes for the physician [26] , which increases the risk of contracting infection from the patient. this could be minimised by following infection control protocols (gowns, masks, gloves and face shields). third, there is an increased chance of cross-infection if the same probe is used in evaluating covid and non-covid patients. this can be prevented by using separate probe covers and low level disinfectants (llds; ethyl or isopropyl alcohol, 70%-90%) after each patient [21] . this was a single-centred study, which may not reflect other ed patient population and owing to the small sample size, there is a possibility of missing few lus characteristics of covid19. this was a single arm observational design, so further studies comparing the lung ultrasound findings of covid and non-covid patient, as well as comparing them with a ct scan of chest, would help in finding specific features unique to covid-19 patients. since more patients with severe symptoms presented to our emergency department, the proportion of mild disease was less in our cohort. it is usual to find 'silent hypoxia' in covid-19 patients, so certain early sonographic findings could have been missed as the patients usually presented late. in our study, the same physicians who classified the disease severity were also the ones who performed the pocus of the patient, which may have introduced bias. lung zones: lung zone -1 extended from 2nd rib to 6th rib in the mid-clavicular line, lung zone -2 extended from 6th rib to 10th rib in the mid-clavicular line, lung zone -3 extended from 4th rib to 12th rib in the mid-axillary line and lung zone -4 extended from 4th rib to 12th rib in the scapular line cell colours were according to the prevalence of lung sonographic findings: 0-10%, white; 10-20% very light grey, 20-30% light grey, 30-40% grey; >40% dark grey with white fonts mild disease: patients with respiratory tract infection, not fulfilling criteria for severe and critical disease, severe disease: any of the following signs or symptoms (shortness of breath, respiratory rate > 30/min or oxygen saturation < 93%), critical disease: patients requiring intensive care for organ failure or invasive ventilation * p -value for chi-square test, which were statistically significant # pairwise comparison of prevalence of lung sonographic findings according to disease severity category showed more bilateral lung involvement in severe/critical disease, as compared to that of mild disease (p -0.034) j o u r n a l p r e -p r o o f journal pre-proof pleural effusion 10 (9.4) 0 (0) 0 (0) 4 (3.8) 4 (3.8) 1 (0.9) 2 (1.9) 8 (7.5) 8 (7.5) deeper consolidation 6 (5.7) 3 (2.8) 3 (2.8) 1 (0.9) 1 (0.9) 0 (0) 0 (0) 1 (0.9) 1 (0.9) j o u r n a l p r e -p r o o f lung ultrasound in the critically ill point-of-care lung ultrasound in patients with covid -19 -a narrative review clinical features of patients infected with 2019 novel coronavirus in wuhan factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in new york city: prospective cohort study clinical course and factors associated with hospitalization and critical illness among covid-19 patients in chicago, illinois. academic emergency medicine n initial emergency department mechanical ventilation strategies for covid-19 hypoxemic respiratory failure and ards sonographic signs and patterns of covid-19 pneumonia clue: covid-19 lung ultrasound in emergency department findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic point-of-care ultrasonography in patients admitted with respiratory symptoms: a single-blind, randomised controlled trial covid-19 outbreak: less stethoscope, more ultrasound global surveillance for human infection with coronavirus disease (covid-19) n.d novel coronavirus: a capsule review for primary care and acute care physicians characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72 314 cases from the chinese center for disease control and prevention rishikesh-06 th -07 th may 2019 -the international council for critical emergency sonography n point-of-care ultrasound in covid-19 pandemic point-of-care lung ultrasound in patients with covid -19 -a narrative review point-of-care lung ultrasound findings in novel coronavirus disease-19 pnemoniae: a case report and potential applications during covid-19 outbreak n point-of-care ultrasound: infection control in the intensive care unit covid-19 pandemic: a two-step triage protocol for emergency department point-of-care ultrasound in covid-19 pandemic can lung us help critical care clinicians in the early diagnosis of novel coronavirus (covid-19) pneumonia? radiology emergency department lung ultrasound findings in novel coronavirus a preliminary study on the ultrasonic manifestations of peripulmonary lesions of non-critical novel coronavirus pneumonia (covid-19) lung ultrasound in acute respiratory distress syndrome and beyond training for lung ultrasound score measurement in critically ill patients the authors did not have any conflicts of interest. the authors did not receive any financial support from any source. the authors did not receive any financial support and have no conflicts of interest.j o u r n a l p r e -p r o o f key: cord-345510-togrmvlk authors: kinney, brad; slama, richard title: rapid outdoor non-compression intubation (ronci) of cardiac arrests to mitigate covid-19 exposure to emergency department staff date: 2020-05-27 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.080 sha: doc_id: 345510 cord_uid: togrmvlk the covid-19 pandemic has introduced numerous challenges for health care professionals including exposing emergency department (ed) staff to the sars-cov-2 virus during cardiopulmonary resuscitation (cpr). recent guidelines from the american heart association (aha) prioritize early intubation with viral filter placement to minimize hospital staff exposure. we propose a novel technique for rapid outdoor non-compression intubation (ronci) of cardiac arrest patients while en route from the ambulance bay to the resuscitation bay to further decrease the risk of viral aerosolization. with the emergence of the covid-19 pandemic, the ethical and moral obligations regarding cardiac arrest care are evolving. 1 while cardiopulmonary resuscitation is the gold standard, only 7.6% of outof-hospital cardiac arrest (ohca) patients survive to discharge. 2 cpr, intubation, and resuscitation of the critically ill expose health care professionals to significant infection risk. 3, 4 this has prompted many to question the standard resuscitation of covid-19 infected cardiac arrest patients, so modification of current resuscitation practices is being explored on many different levels. 5 we present a case of an outdoor non-compression intubation of a patient in cardiac arrest to minimize covid-19 exposure to staff while still providing standard advanced cardiac life support (acls). a 75-year-old male was found by family unresponsive in cardiac arrest and was last seen well one hour prior to arrival. ems initiated cpr and transported with basic life support (bls) in process and a fifteenminute estimated time of arrival (eta). in the ed, we conducted a pre-resuscitation briefing and prepared the appropriate equipment in advance. we donned airborne ppe (personal protective equipment), papr (powered air-purifying respirator) hoods, and placed a video laryngoscope (vl) in our ambulance bay. the ett (endotracheal tube), rigid stylet, syringe, and ventilator tubing (inline suction, corrugated tubing, viral filter, end tidal co2) with bvm ( figure 1 ) were placed in the vl accessory basket in the intubation staging area ( figure 2 ). this setup is used because it is transferable between vents without clamping the ett, minimizes the risk of gross viral filter contamination, and utilizes in-line suction as well as end tidal co2 monitoring. j o u r n a l p r e -p r o o f upon ems arrival, cpr continued until the stretcher was positioned in our intubation staging area. we discontinued cpr momentarily, inserted the ett, inflated the ett cuff, and connected the viral filter setup. we resumed cpr immediately and provided ventilations with a bvm. the intubation was performed in less than fifteen seconds. we then transported the patient to our decontamination (decon) room where resuscitation continued. after multiple rounds of acls, resuscitation was terminated due to futility. later, after discussion with the family, the patient had complained of "coldlike" symptoms and worsening shortness of breath for the previous three days. during the covid-19 pandemic, intubation is the highest risk ed procedure, 6,7 ,8,9 and continuing cpr during intubation likely increases exposure risk. non-compression intubation is suggested by ed resuscitation experts and the american heart association (aha) to minimize covid-19 exposure to staff. before this pandemic, compression interruption was anathema except for ventilation and pulse and rhythm checks. 10 considering the risks to staff, novel approaches to intubation during cardiac arrests should be considered. to avoid unknown and high-risk exposures, our ed currently treats all cardiac arrests as if covid-19 positive. prior to ems arrival, our ed staff dons airborne ppe consisting of an n95 respirator, goggles, gown, and gloves. 11 additionally, those managing the airway and those performing compressions don papr hoods. 12 all cardiac arrests are resuscitated in our negative pressure decon room. 13 theoretically, once intubated with the ett cuff inflated and viral filter in place, viral exposure is minimized and contamination of the surrounding area is diminished. 14 in order to even further mitigate staff exposure, we decided to trial non-compression intubation outdoors in a well-ventilated area with cuff inflation and viral filter placement prior to ed entrance. our experience revealed several key points to keep in mind prior to performing ronci. while seamless teamwork, leadership, and communication are necessary during resuscitations, the current pandemic emphasizes the importance of refining these techniques. 15 communication suffers while wearing full ppe and papr hoods; so pre-assigning roles, practicing specific procedures, and utilizing simplified means of communication are indispensable. to avoid lengthy interruptions of cpr and worsening mortality, 10 we recommend limiting the ronci attempt to less than 10-15 seconds. if successful intubation cannot be performed within this timeframe; we recommend aborting the attempt, resuming cpr, and attempting later in a controlled environment where more equipment is available. supraglottic airways can also be considered if intubation is unsuccessful. 5 the aha recommends that the "provider…with the best chance of first-pass success" should perform the intubations in suspected covid-19 infected patients in cardiac arrest. 5 we suggest positioning ronci equipment ergonomically prior to ems arrival, and adjusting the ems stretcher height to optimize first-pass success. recognizing the limitations of this technique and applying it to the correct patient populations is of utmost importance. while no standard definition of a difficult airway exists, providers should quickly recognize airways with a high likelihood of first pass failure (massive upper gi bleeds, neck trauma, severe morbid obesity, etc.) and move directly to the resuscitation bay. 16 j o u r n a l p r e -p r o o f finally, some practical considerations that may preclude this technique include adverse weather conditions, suboptimal ambulance bay layouts, and short ems arrival times. in this case, we discuss a novel technique for intubation to decrease staff exposure to aerosolized covid-19. we found that this technique is easily performed, requires no specialized equipment, and provides an early closed system to minimize aerosolization. in the future, a more advanced setup including portable suction will likely be utilized. fair allocation of scarce medical resources in the time of covid-19 predictors of survival and neurologic outcome for adults with extracorporeal cardiopulmonary resuscitation: a systemic review and meta-analysis covid-19 and the risk to health care workers: a case report the workers who face the greatest coronavirus risk -the new york times interim guidance for basic and advanced life support in adults, children, and neonates with suspected or confirmed covid-19: from the emergency cardiovascular care committee and get with the guidelines®-resuscitation adult and pediatric task forces of the aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review detection of sars-cov-2 in different types of clinical specimens staff safety during emergency airway management for covid-19 in hong kong expert recommendations for tracheal intubation in critically ill patients with noval coronavirus disease american heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care clinical management of severe acute respiratory infection when covid-19 is suspected (v1.2) practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-ncov) patients cdc. management of patients with confirmed 2019-ncov | cdc ventilation of sars patients: lessons from the 2003 sars outbreak teamwork and leadership in cardiopulmonary resuscitation practice guidelines for management of the difficult airway key: cord-338814-r9ym1h3m authors: li, yan; zhang, kai title: using social media for telemedicine during the covid-19 epidemic date: 2020-08-17 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.007 sha: doc_id: 338814 cord_uid: r9ym1h3m nan measures to prevent the spread of the epidemic [1] [2] [3] . as the first country to discover covid-19, china has taken strict precautionary measures. on january 23, 2020, china raised the national public health emergency level to the highest level [1] . these measures include closing schools and entertainment venues, prohibiting public gatherings, restricting access to and from the city, and so on. the chinese government strives to raise public awareness of prevention and protection by providing daily monitoring and updates on websites and social media [4] . nevertheless, covid-19 is still a danger in china and other countries. social media played an essential role during the covid-19 epidemic. the government should support and encourage medical personnel to participate in science education on social media. because the strict quarantine measures make it difficult for patients to see a doctor, it is urgent to establish an appropriate telemedicine and appointment system. at the same time, social media can also promote the development of telemedicine. covid-19 is officially a pandemic. although the impact of the final course of covid-19 is not yet fully determined, the disease is not only possible, but is likely to produce a serious disease, which may overwhelm the health care infrastructure. the emergence of the virus pandemic will make the public health system and community health service institutions face special and lasting epidemic prevention situation. government officials and policy makers should try their best to avoid the shortage of medical resources. the covid-19 pandemic made us realize that if an outbreak in a region of the world is not properly handled, people around the world will be threatened [4, 5] . the strict isolation strategies have affected and challenged different medical areas. in many countries, dentists were forced to stop working during quarantine until further discomfort and fear of the epidemic can also affect the psychological state of patients, leading to anxiety and anger [4, 7] . some chronic otolaryngology diseases require long-term medication. because some drugs are prescription drugs, they are not available in pharmacies. the lack of drugs and the pain of illness also increase the anxiety of patients [7] . in addition, the multidisciplinary treatment needs of suspected and diagnosed patients with covid-19 pneumonia are challenging to meet. since there are very few telemedicine projects created temporarily, patients may have to pay. we think social media can solve this difficult problem, such as facebook and an investigation of transmission control measur es during the first 50 days of the covid-19 epidemic in china is traditional chinese medicine useful in the treatment of covid-19? the ethics of covid-19 clinical trials: new considerations in a controversial area access to lifesaving medical resources for african countries: covid-19 testing and response, ethics, and politics the mental hea lth consequences of coronavirus disease 2019 pandemic in dentistry. disa ster med public health prep the authors received no financial support for the research, authorship, and/or publication of this article. the authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. key: cord-353698-gj8sx3zy authors: bibiano-guillen, c.; arias-arcos, b.; collado-escudero, c.; mir-montero, m.; corella-montoya, f.; torres-macho, j.; buendía-garcia, m.j.; larrainzar-garijo, r. title: adapted diving mask (adm) device as respiratory support with oxygen output during covid-19 pandemic date: 2020-10-28 journal: am j emerg med doi: 10.1016/j.ajem.2020.10.043 sha: doc_id: 353698 cord_uid: gj8sx3zy nan at the end of 2019, several cases of pneumonia were identified in wuhan (hubei, china) [1], caused by a new orthocoronavirinae, commonly known as coronavirus, from the coronaviridae family. in january 2020, there was a public health emergency declaration [2] and, as of march 2020, a pandemic [3, 4] . at present, more than 2 million cases have been confirmed globally (2.160 .2017 april 18th) [5] [6] [7] [8] [9] . in spain, the first spots of epidemiological interest were identified in madrid. some of them were registered in the sanitary region where both hospital universitario infanta leonor and virgen de la torre hospitals belong. the first pcr-positive patient was detected on march 4 th . after two weeks, on 18 th march, the number of positive cases increased to 302, and 41 patients died. by 1 st april, one month after the outbreak, the total number of cases was 1714. these data confirmed the explosive progression of the pandemic and the high mortality of patients who were hospitalized and made it necessary to implement several and different therapeutic measures to try and revert the catastrophic progression of this infection. the most extended therapeutic approach for covid-19 is based on two main strategies [10] [11] [12] [13] : pharmacological treatment directed toward several physiological targets (viremia, immunological reactions, prothrombotic reactions) and hemodynamic and respiratory support with positive end-expiratory pressure (peep) in addition to mechanical ventilation. this is vitally necessary until pharmacological treatment or patient immune responses become effective. china and italy have already described that acute respiratory distress syndrome (ards) is the most common manifestation in the clinical course of covid-19 pneumonia [11] [12] [13] [14] ; however, this syndrome has a different progression than other j o u r n a l p r e -p r o o f respiratory diseases. the first-choice treatment for ards is mechanical ventilation (mv) with the use of orotracheal intubation (oti). the ards mortality rate is over 50%, and the delay in this procedure is related to an even worse prognosis [15, 16] . the main limiting factors that healthcare systems must face when handling these critical patients are the limited access to ventilators and icu resources and the fact that they are already overwhelmed by massive hospitalization due to respiratory distress and oti needs [17, 18] . this is why current lines of work are focused on developing respiratory support alternatives that will gain time or allow the maintenance of an acceptable respiratory status until patients can access the icu [19, 20] . in the absence of approved mechanical devices, such as continuous positive airway pressure (cpap), positive end-expiratory pressure (peep) devices are being used [14, 16, 21] . in this paper, we describe our experience with the adaptation of diving masks (figure 1 ) and predesigned and 3d-printed pieces (annex) that work as respiratory peep valves and high-flow oxygen connectors. during the inspiratory phase, oxygen reaches the fitted mask via a high-flow tube connected to a flowmeter at an outlet on a high-pressure hospital circuit or in a portable oxygen bottle. the residual volume of the mask becomes a reservoir. during the expiratory phase, the peep valve resists airflow. the exhaled air flows decontaminated through an n99 high-efficiency filter, reducing the possibility of contagion by viral aerosolization. the main objective was to assess the efficacy of this alternative prototype for respiratory support in the context of the covid-19 pandemic. the secondary outcomes were the clinical profiles of patients who could benefit from this device, as well as the safety parameters and potential adverse events. a descriptive case series study of twenty-five patients with acute respiratory syndrome secondary to sars-cov2 infection was performed at a spanish center, hospital universitario infanta leonor of madrid, between march 30 and april 18, 2020. we tested the easybreath first-generation snorkel mask (decathlon©) adapted with 3dprinted appliances as a respiratory support device with oxygen output and a peep valve. all patients provided written informed consent, and the study was approved by the hospital committee for medical and health research ethics. there were a total of twenty-five patients: twenty-one men and four women. the demographics, baseline characteristics and comorbidities are shown in table 1 . we established two clinical settings for the use of an adapted diving mask (adm) at the emergency department: 1. patients with an oxygen saturation under 93% and oxygen reserve to 15 l. 2. patients using pulmodyne® cpap who presented with mild to severe intolerance to their interface or with an oxygen saturation under 92% despite maximum oxygen airflow. the mask was used with interrupted discontinuous character only to feed or hydrate the patient, aspirate secretions, if necessary, and administer artificial tears in the case of dry eye. in the absence of this nursing care, the patient was advised to maintain mask therapy for as long as possible. severe clinical status was established when radiographic pulmonary alterations and serologic alterations such as lymphocyte count, transaminases, ldh and d-dimer were present. to assess the initial response of patients, we analyzed two variables: 1. oxygen saturation improvement by comparing previous measurements and those immediately after oxygen saturation to the use of the mask. a. qualitative variable: at least a 3-point improvement in oxygen saturation (yes/no). b. continuous variable: improvement in mean-score mean from pre-mask saturation values. 2. arterial blood gas analysis (abga) at one hour. gas parameters were measured after one hour of mask use. to assess patient improvement, we used the following variables: the medical records of patients were analyzed by the research team of the emergency department, hospital universitario infanta leonor, madrid. epidemiological, clinical, laboratory, radiological and treatment outcome data were obtained via data collection forms from the electronic medical records. the data were reviewed by a trained team of physicians. the recorded information included demographic data, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, and treatment measures. descriptive statistical analysis was performed using ibm spss statistics version 22 software (ibm corporation usa). in this case series, the most common radiological pattern was the bilateral interstitial pattern (92,85%), followed by the multilobular pulmonary consolidation pattern (7.14%). a total of 3.57% of patients had less than 1500/µl lymphocytes, 85.7% had less than 150000/µl platelets, 78.5% had over 250 ldh u/l, 46.4% had d-dimer levels above 500 ng/ml, and 82.1% had a got over 40 u/l. the mean baseline oxygen saturation on admission was 83.6%, distributed in severity ranges as shown in table 2 . there were two patients who had missing data. the distribution of patients according to the clinical setting is described in table 2 . adm use was higher in patients with an oxygen saturation under 93% with reservoir masks at 15 lpm (18 patients). oxygen saturation was measured before initiating adm therapy. the mean value was 90.24 %, and the patient distribution was made according to severity at saturation levels, as shown in table 2 . after adm initiation, patients had a very positive initial response ( table 3 ). the immediate saturation value after adm placement was 95.8%. in twenty-one patients, the saturation improvement was 3 or higher. the mean po2 after one hour of adm treatment was 93.75 mmhg, as measured by arterial abga (in five patients, we were not able to collect these data), the mean pco2 was 40.91 mmhg, and all patients surpassed the 50 mmhg limit. table 4 shows the different variables used to analyze the improvement in the intervention and the mean value of all oxygen saturation measurements for all days that adm therapy was used in those patients who prolonged its time of use. more than 50% of patients tolerated the mask for 24 hours, switching to 3-hour minimum rotational use in combination with other therapies or devices. the main cause of adm cessation was physical intolerance (nine patients). eight patients needed invasive mechanical ventilation due to disease progression. finally, five patients experienced clinical respiratory improvement. during the time of the study, eight patients died, five of whom were dismissed for icu admission for prevalent comorbidities and advanced disease stage. three of the patients who were admitted to the icu for invasive mechanical ventilation died. there were no adverse events related to oxygen system failure during clinical use of the adm device or any eye or skin adverse events. four patients presented with isolated mild hypercapnia (pco2 > 45 mmhg<5° mmhg) during adm use, two of whom presented in the first hour of therapy and two during the adm rotation period with other therapies and interfaces, without any additional clinical or analytical repercussions. the mask was not indicated in any patients who, in their baseline situation, already had hypercapnia of any degree or respiratory acidosis. one patient presented with respiratory acidosis (ph <7.35) and moderate hypercapnia (pco2> 50 mmhg) during mask use. this patient was not considered for icu care due to late disease progression and poor respiratory dynamics, which ended in death a few hours later (table 5 ). the adapted easybreath™ system is an efficient and safe alternative for respiratory support in the shortage of official devices in the current state of the pandemic. it has already been described that covid-19 disease has two differentiated phases: initial pulmonary alveolar affectation caused by viral access to ac2 receptors [22, 23] and, second, an inflammatory phase mediated by macrophages [24] . both have a common characteristic, hypoxemia, and this is why choosing the best respiratory support as soon as possible is of utmost importance for the clinical course of patients. regrettably, sanitary activity during the covid-19 pandemic is conditioned by what the who has defined as "multiple victim incidence", where more patients are generated than those who can be treated in optimal conditions [18] [20] . for this j o u r n a l p r e -p r o o f reason, many of the recent publications reference overwhelmed healthcare systems and compare the current situation to battlefield medicine practice. the first-choice treatment for ards is mechanical ventilation (mv) with the use of orotracheal intubation (oti) [14] [15] [16] 21] . in the clinical event of resource and device shortage (full icu, respirator shortage and lack of healthcare professionals), noninvasive respiratory support can be considered a valid alternative despite the worsening prognosis already published [11, 21, 25] . both nimv and cpap or high-oxygen airflow therapy can be administered to patients by several devices depending on the availability and indication: oronasal masks, facial masks or helmets [26] [27] [28] . through release valves, less nebulization is produced by helmets and the highest with oronasal masks. it is of high importance to take into account these devices in the covid-19 pandemic context, as potential viral contamination to patients is caused by aerosolized particles, which is a limiting factor, as well as the limited availability of the cpap/bipap device [29] [30] [31] . with the use of the easybreath™ mask (adm), we can address both issues. on the one hand, adms minimize contamination in the patient surroundings, as the facial silicone almost completely seals the faces of patient and because it is a semi-open device with just one output through the exhalatory port where air comes out already filtrated by a highly efficient n99,99 filter. this prevents exposure to other patients and healthcare professionals [29, 32, 33] . on the other hand, the technical requirements for adms are minimal: an oxygen flowmeter with as much oxygen airflow possible. all necessary pieces needed for the adaptation of adms have been designed by a multidisciplinary team of engineers and doctors (see annex). 3d impression technology for medical use needs to work with nontoxic, inert materials that would prevent leaching of one or more substances contained in the adaptor that was originally of powder base. to avoid this and at the same time comply with regulatory rules en 5356 and en 13544, the preferred material is pa12 (sls) [34, 35] . our results show a rapid improvement in oxygen saturation maintained in time without any adverse events. in addition, adaptation of the adm is safe for two main j o u r n a l p r e -p r o o f reasons. first, a 3d anti-suffocation valve adapted to our device allows for patients to inspire atmospheric air in case there is a pressure drop in the system (accidental decoupling of the oxygen source). second, there was no hypercapnia or respiratory acidosis in any of the follow-up tests performed in patients, meaning that rebreathing did not take place. the mild hypercapnia that was detected in some patients may pertain to the highoxygen airflow administered (fio2 administered close to 100%). this may also occur with common reservoir masks. therapy should be suspended only if hypercapnia progressively increases or increases to moderate hypercapnia levels (pco2> 50 mmhg) or if it is associated with acidosis of any degree (ph <7.35). in other words, patients should remove their masks if hypercapnia is present, despite being mild, if it increases in the first hours of use, if it is moderate or if any of the above factors are also associated with respiratory acidosis. patients will be able to maintain masks with stable mild hypercapnia in the first 3 hours and if a lack of acidosis remains. one alveolar recruitment technique that helps patient oxygenation in icus for patients with ards is pronation [13] . few studies have shown that the pronation maneuver in a non-icu setting in patients treated with any type of respiratory support in the emergency room or who are hospitalized may improve the ventilatory/perfusion gradient of lungs and, therefore, hypoxemia [16] . therefore, pronation, when necessary, is best tolerated by patients wearing masks. in our series, patients had low saturation levels even in pronation and used adms with up to >90% oxygen saturation in the supine position and with head elevated to 30 degrees. some starting resources are necessary to be able to adapt to masks, but once the adaptation process is complete, masks can be completely reused by another patient, except for a high-efficiency filter following the matachana sequence designed for our center: 1. enzymatic detergent wash (mediclean forte™) 2. rinse. 3. wash the disinfector at 80° for 50 minutes to guarantee ao=3000. this is the reference value used for thermoresistant germs, including hepatitis b or mycobacteria. 4. 85° drying turbine. this study has some limitations. the main limitation is derived from the design. we did not have a control group, as this was not possible in the critical clinical setting that has developed. therefore, we cannot compare respiratory support with other therapies with the same characteristics, which would have been highly desirable. additionally, 3d printing allows for the creation and testing of many prototypes in a rapid manner, but for midterm provisions and in a global pandemic setting, the final solution should be able to increase the production rate to respond to high demand when 3d printing is not available, perhaps via injection molding. injection molding will make it possible to produce thousands of pieces per day at a lower cost, although initial investment (design and production of the mold) needs to be perfectly validated before starting the production process. another disadvantage of 3d printing is that the production error has to be reduced to ±0,005 mm with a surface finish of 0,4 μm. this is not possible to guarantee with 3d printing methods, but it would be possible to produce with injection molding. we are aware of the limitations of the adm proposal as an alternative to respiratory support, and assuming its use in pandemics and the deep shortage of certified alternatives, we can conclude that it complies with clinical requirements to be produced in other centers with limited resources [17] [18] [19] 36] , especially in developing countries. this is a therapy that provides an adm device; it only requires oxygen connection with a flowmeter with a minimum airflow of 15 lpm. it has also shown a lack of significant adverse events, presenting an optimal initial tolerability in twentythree patients, and we propose it as a more comfortable interface option for those patients highly dependent on noninvasive respiratory support. j o u r n a l p r e -p r o o f j o u r n a l p r e -p r o o f mild hypercapnia (%) 20 skin irritation (%) 0 eye irritation (%) 0 j o u r n a l p r e -p r o o f who declares covid-19 a pandemic covid-19: towards controlling of a pandemic covid-19 and community mitigation strategies in a pandemic first case of 2019 novel coronavirus in the united states estimation of covid-19 outbreak size in italy outbreak investigation for covid-19 in northern vietnam covid-19 and italy: what next? lancet. lancet publishing group covid-19 in europe: the italian lesson novel 2019 coronavirus sars-cov-2 (covid-19): an overview for emergency clinicians clinical course and outcomes of critically ill patients with sars-cov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study xiaobo yang* hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china management of respiratory failure due to covid-19 respiratory support for patients with covid-19 infection recommendations for endotracheal intubation of covid-19 patients respiratory physiotherapy in patients with covid-19 infection in acute setting: a position paper of the italian association of respiratory physiotherapists clinical ethics recommendations for the allocation of intensive care treatments in exceptional, resource-limited circumstances: the italian perspective during the covid-19 epidemic the response of ilan's emer ency edical system to the ovid-19 outbreak in italy hospital surge capacity in a tertiary emergency referral centre during the covid-19 outbreak in italy emergency departments and the covid-19 pandemic: making the most of limited resources clinical consensus recommendations regarding non-invasive respiratory support in the adult patient with acute respiratory failure secondary to sars-cov-2 infection structural basis of receptor recognition by sars-cov-2. nature receptor recognition by the novel coronavirus from wuhan: an analysis based on decade-long structural studies of sars coronavirus covid-19: consider cytokine storm syndromes and immunosuppression high-flow nasal cannula may be no safer than noninvasive positive pressure ventilation for covid-19 patients helmet cpap to treat acute hypoxemic respiratory failure in patients with covid-19: a management strategy proposal treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: a randomized controlled trial high-flow nasal cannulae for respiratory support in adult intensive care patients protecting health-care workers from subclinical coronavirus infection high-flow nasal cannula for covid-19 patients: low risk of bio-aerosol dispersion more awareness is needed for severe acute respiratory syndrome coronavirus 2019 transmission through exhaled air during non-invasive respiratory support: experience from china staff safety during emergency airway management for covid-19 in hong kong activities of daily living after hip fracture: profile and rate of recovery during 2 years of follow-up three-dimensional (3d) printing of polymer-metal hybrid materials by fused deposition modeling. materials (basel) enhancement of thermal, mechanical and physical properties of polyamide 12 composites via hybridization of ceramics for bone replacement how emergency departments prepare for virus disease outbreaks like covid-19 acknowledgement e ac no led e ristina rce for her re ision and translation of the manuscript and anuel ere -espa a uniesa d, for their support in the early phases of covid 19 pandemia. the authors want to acknowledge the effort and creativity in the design of the adapting parts of the mask to juan manuel canalejo-bautista (airbus) and alberto molina parga (ct engineers) key: cord-354468-bew35s8q authors: margus, colton; sondheim, samuel e.; peck, nathan m.; storch, bess; ngai, ka ming; ho, hsi en; she, trent title: discharge in pandemic: suspected covid-19 patients returning to the emergency department within 72 hours for admission date: 2020-08-18 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.034 sha: doc_id: 354468 cord_uid: bew35s8q introduction: coronavirus disease 2019 (covid-19) has led to unprecedented healthcare demand. this study seeks to characterize emergency department (ed) discharges suspected of covid-19 that are admitted within 72 h. methods: we abstracted all adult discharges with suspected covid-19 from five new york city eds between march 2nd and april 15th. those admitted within 72 h were then compared against those who were not using descriptive and regression analysis of background and clinical characteristics. results: discharged ed patients returning within 72 h were more often admitted if suspected of covid-19 (32.9% vs 12.1%, p < .0001). of 7433 suspected covid-19 discharges, the 139 (1.9%) admitted within 72 h were older (55.4 vs. 45.6 years, or 1.03) and more often male (1.32) or with a history of obstructive lung disease (2.77) or diabetes (1.58) than those who were not admitted (p < .05). additional associations included non-english preference, cancer, heart failure, hypertension, renal disease, ambulance arrival, higher triage acuity, longer ed stay or time from symptom onset, fever, tachycardia, dyspnea, gastrointestinal symptoms, x-ray abnormalities, and decreased platelets and lymphocytes (p < .05 for all). on 72-h return, 91 (65.5%) subjects required oxygen, and 7 (5.0%) required mechanical ventilation in the ed. twenty-two (15.8%) of the study group have since died. conclusion: several factors emerge as associated with 72-h ed return admission in subjects suspected of covid-19. these should be considered when assessing discharge risk in clinical practice. novel coronavirus disease 2019 (covid-19) has emerged as an extraordinary challenge to the healthcare system. early case fatality estimates for patients with covid-19 are between 0.6% and 3.5%, 1 with 3.2% reported as having required endotracheal intubation in china. 2 as covid-19 cases continue to globally, [3] [4] [5] [6] hospitals have needed to adapt their usual practices, with increased emphasis on the emergency department (ed) role in directing resources to where they are most needed. [7] [8] [9] [10] during the study period, the availability of rapid testing for covid-19 remained limited in many parts of the united states, with many hospitals, including the study sites, utilizing these scarce tests only for patients upon admission. instead, clinical suspicion of covid-19 guided medical decision-making. a number of factors have been proposed as having an association with morbidity and mortality among those hospitalized: increased age, male sex, malignancy, diabetes, hypertension, chronic obstructive pulmonary disease, bilateral pneumonia, and inflammatory changes such as low platelets and increased transaminases, lactate dehydrogenase, c-reactive protein, and d-dimer. [12] [13] [14] for ed patients deemed stable for discharge rather than admission, however, minimal guidance exists to clarify a clinical approach to patients who remain under investigation. in this paper, we focus on ed disposition decision-making in new york city during the covid-19 pandemic, by identifying patients suspected of covid-19 who are discharged yet ultimately require hospital return and admission within 72 hours. this study seeks to describe the historical, clinical, and demographic characteristics that are associated with an unscheduled return to the ed. was employed to determine significant predictors of 72-hour return admission. our hospital"s institutional review board reviewed and approved this research. we analyzed all ed visits from patients aged 18 years and above who raised clinical suspicion for covid-19 between march 2nd and april 15th. an encounter raising clinical concern for covid-19 was defined as (1) laboratory sars-cov-2 real-time reverse transcription polymerase chain reaction (rrt-pcr) or nucleic acid amplification (naa) testing from nasopharyngeal swab specimens regardless of result, (2) clinician-entered discharge instructions pertaining to confirmed or suspected covid-19, and/or (3) a self-isolation discharge order. case subjects were identified as those patients suspected of covid-19 and discharged from the ed but who returned to an ed within the system in 72 hours and required admission. control subjects were identified as those patients suspected of covid-19 and discharged from the ed who did not require admission within the system in 72 hours. we then created a nested case-control with one control per case using single-iteration random number generation. this random sampling of controls was then compared to the larger cohort to confirm representativeness. the primary outcome of this study was hospital admission within 72 hours of ed discharge. data were abstracted from the hospital"s electronic medical record system (hyperspace, february 2019, epic systems corporation, verona, wi). zip codes were used to determine median household income through existing united states census data. 17 in order to group listed health problems, past medical history was evaluated for key comorbidities and their associated medical terms as determined by the clinician authors. for a nested case-control comparison of clinical features from the initial ed visit, three emergency physicians each abstracted an equal and random selection of patients from case and control groups. a brief training session was provided prior to data collection, and supervision was maintained throughout the abstraction process. data was collected with assistance from the redcap electronic data capture tool, 18 and a sample from each reviewer"s panel was subsequently reviewed by a separate abstractor to ensure uniform data abstraction. vital signs out of reportable norm were treated as missing. symptoms and laboratory values were noted based on previously reported manifestations of pandemic coronavirus. 19 chest x-ray reports were manually categorized by the presence of acute pulmonary pathology as well as by multifocal distributions based on the diffuse pattern often seen in covid-19. 20, 21 data analysis prism (version 8.4.2, graphpad software, san diego, ca) was used for all descriptive statistics. continuous variables were assessed with the unpaired welch"s t-test if normally distributed and the mann whitney u test if not. the χ 2 test was employed for all categorical variables unless the smallest expected value within a given contingency table was less than five observations. a two-sided α of less than 0.05 determined statistical significance. significant exposures with respect to the cohort group were then included in multivariate logistic regression using rstudio (version 1.2.5042, rstudio, boston, ma). variables involving the provision of care were excluded from the model. confidence intervals (ci) of the odds ratio (or) were bounded at the 0.025 and 0.975-quantiles. of the 139 case subjects discharged with suspicion for covid-19 who returned for admission within 72 hours, 90 (64.7%) were male, 31 (22.3%) identified as african american, 105 (75.5%) listed english as their preferred language, and 58 (41.7%) relied on medicare or medicaid coverage. average age was 55.4 ±15.6 years, body mass index was 29.0 ±6.9 for whom it was listed, and median income, as determined by zip code, was $63,005 ±$25,028. the following comorbid conditions were reported as past medical history for ten or more subjects: asthma (14.4%), cancer (9.4%), chronic obstructive pulmonary disease (7.2%), diabetes (25.2%), hypertension (38.8%), and renal disease (7.2%). for their initial ed encounter, 41 (29.5%) subjects came by ambulance, and 25 (18.0%) were triaged at an emergency severity index (esi) ≤2. length of ed stay was 5.6 ±4.2 hours. chest x-rays were obtained for 95 (68.3%) and 115 (82.7%) subjects on the initial and return encounters, respectively. fifty-eight (61.1%) chest x-rays were abnormal on the initial visit, compared with 102 (88.7%) on return. seventy-eight (56.1%) subjects had chest x-rays obtained on both the initial and return visit, enabling temporal comparison: twenty-one (26.9%) became abnormal, and 21 (26.9%) became multifocal within 72 hours. upon 72-hour ed return, 91 (65.5%) of the study group required oxygen supplementation. sixteen (11.5%) of those deemed safe enough for discharge less than 72 hours prior required engaging a critical care team or intensive care unit on reevaluation, and 7 (5.0%) required endotracheal intubation in the ed or prehospital setting. as of may 8th, 22 subjects (15.8%) had died. when suspected covid-19 discharges with 72-hour return admission were compared to the cohort of those without, men were more likely to be admitted within 72 hours (64.7 vs. 50 a subgroup of the 7,294 control cohort equal in size to the 139 case subjects was prepared in order to compare manually abstracted clinical data pertaining to the initial ed encounter. in preparing this nested control subgroup, we first evaluated the 139 randomly selected controls against the rest of the control cohort and found no statistical difference in baseline characteristics (supplement a). compared to the 139 nested controls, the study group more frequently reported vomiting (13.7 vs. 4.3%, p=0.0064), diarrhea (22.3 vs. 10.8%, p=0.0098), abdominal pain (10.1 vs. 3.6%, p=0.0324), and dyspnea (47.5 vs. 35.2%, p=0.0384) among their initial visit"s presenting symptoms. of treatments provided, only the administration of antibiotics was found to be associated with return admission within 72 hours (16.5 vs. 7.9%, p=0.0280). fever, defined as a temperature ≥38°c (35.3 vs. 18.7%, p=0.0019), and tachycardia, defined as a heart rate ≥100 beats per minute (41.0 vs. 29.5%, p=0.0446), were the two vital sign abnormalities that demonstrated a significant difference. home angiotensin-converting enzyme (ace) inhibitor or angiotensin receptor blocker (arb) use was not significant. 124.6 ±59.5 mg/dl, p=0.0364), lower lymphocyte counts (1.1 ±0.5 vs. 1.3 ±0.5 k/μl, p=0.0202), and lower platelet counts (207.6 ±86.0 vs. 266.0 ±110.5 k/μl, p=0.0084) on the first ed encounter. we did not find a significant difference in brain natriuretic peptide, c-reactive protein, creatinine, d-dimer, lactate dehydrogenase, lactic acid, procalcitonin, or troponin. in conducting multivariate logistic regression of the case subjects against the full control cohort, one control was omitted due to missing data. age was found to increase the odds of return admission within 72 hours ( .044) were also found to be predictive. with a documented 30,903 hospitalizations and 7,563 deaths within the study period between march 2nd and april 15th, 22 the burden of covid-19 on the new york city healthcare system has been significant. while efforts to understand disease progression among hospitalized patients with confirmed covid-19 are invaluable, the ability to safely discharge a patient is of critical importance to both ed resource stewardship and clinical practice. this analysis of suspected covid-19 patients aimed to describe key features of the initial ed visit that may ultimately influence the likelihood of ed return for admission within 72 hours of discharge. prior to the emergence of covid-19, several studies assessing return admission indicated associations with increasing age, disease severity, ambulance transport, gastrointestinal or infectious disease symptoms, and prolonged time in the ed. [23] [24] [25] [26] [27] many of these previous conclusions also appear to remain significant to 72-hour return admission in the setting of covid-19. gastrointestinal symptoms predominate, for example, while increasing age, triage acuity, and ed length of stay all remain significant. covid-19 often presents with respiratory features, such that the association with dyspnea and the predictive value of chronic obstructive pulmonary disease were both to be expected. 28 yet, unlike a temperature over 38°c and a heart rate over 100 beats per minute, the initial triage vital signs of blood pressure, respirations over 20 breaths per minute, and oxygen saturation less than 95% on room air did not achieve significance for return admission. this is perhaps because of their role in the initial disposition decision, with hemodynamically unstable or hypoxic patients unlikely to be sent home. 29 the finding may lend credence to alternative ed clinical assessments of respiratory status, such as single breath counting [30] [31] and desaturation with ambulation. 32, 33 despite the clinical priority of respiratory symptoms, it is noteworthy that gastrointestinal symptoms were significantly associated with admission within 72 hours of discharge. vomiting and diarrhea are not only more readily managed through outpatient supportive care than are respiratory complaints, but, when seen in covid-19, they may also present earlier and suggest a longer disease course in which the patient is more likely to decompensate. 34, 35 medical history also appears to be associated with 72-hour return for admission. glucose level and diabetes history, for example, were both found to be significant, consistent with a previously shown association between glycemic dysregulation and mortality. 12, 14 differences seen with histories of cancer, diabetes, and hypertension all point to a possible predisposition with metabolic derangement. notably, we did not find an association with body mass index, despite previously reported significance. 36 however, with body mass index available for only 23.7% of cases and 21.4% of controls, and with many of those values not updated during the ed visit, our results may not have accurately captured a possible association. we also did not find an association with renal disease. we theorize that patients with chronic kidney disease may have warranted admission on initial visit and that our timeframe of 72 hours may have been too short to accurately capture patients who develop acute kidney injury. 37 we did not include laboratory testing in our initial meta-analysis due to infrequent testing, however for those that did have them drawn on the initial ed encounter, lower lymphocytes and lower platelets appeared associated with return admission. this corroborates meta-analysis and case series data suggesting an association with disease severity in both. 19, 38, 39 chest x-ray remains central to early detection of disease. 21 in our study, abnormal x-rays, particularly those reported with multifocal distributions, were significantly associated with return admission in the next 72 hours. curiously, even the decision to obtain a chest x-ray in the first place proved significant, possibly indicating the overall clinical picture, or perhaps a degree of diagnostic uncertainty, not otherwise conveyed. while 26.9% of normal chest x-rays within the study group progressed to abnormality when repeated within 72 hours, 1 of 3 (33.3%) controls progressed similarly, impeding meaningful conclusions on the utility of this kind of radiographic screen. return after ed discharge has been attributed to disease course, 40 but this study has also shown that patients on federal health insurance and preferring a language other than english were more likely to return for admission within 72 hours. medicare is highly correlated with age, which likely explains why this categorical variable was ineffective in the regression analysis. even so, these characteristics suggest a possible link to socioeconomic status that has previously been associated with return admission after ed discharge. 41 this study has several limitations. while not considered a favorable outcome, ed return admission does not necessarily indicate an error in disposition decision. 42 all ed discharge considerations include the potential for disease progression. in times of resource scarcity, discharging patients with higher than normal potential for return admission may be necessary in order to prioritize interim bed availability. additionally, timeframes longer than 72 hours may also serve as appropriate cutoffs for reviewing ed return admissions. 43 however, the decision to rely on 72-hour return was made based on its established use as a healthcare quality metric for patient recidivism. [44] [45] [46] [47] additional limitations pertain to the extent to which the cohort prepared here adequately captures suspected covid-19 cases. during the study period, health system policy changed, ultimately advising against routine viral testing in favor of discharge guidance only for those "persons under investigation" (pui), patients who could be safely discharged despite risk factors or symptoms consistent with covid-19. 48 we therefore relied on a combination of covid-19 testing, discharge instructions, and a covid-19-specific "self-isolation at home" discharge order as surrogates for covid-19 suspicion. mirroring the ambiguity ed clinicians currently face, this study likely included some patients without disease and neglected a portion of infected individuals without typical symptoms, of which there are many. 49 even among cases included in this study, still some may have subsequently died in the community or re-presented to outside hospitals, 50 preventing analysis of their disease progression. finally, the very immediacy of the pandemic necessitating study of this kind also limits its generalizability. limiting analysis to the study period prevented comparison to pre-pandemic 72-hour returns. in manually abstracting data pertaining to individual ed visits, we opted for representative sampling of a nested control group aggregated from five hospitals, where case and control groups are more often selected from the same set of data and not from pooled data. although not significantly different from the larger cohort, these nested controls may nonetheless lack true representativeness. this concern for introducing additional bias obligated their exclusion from the regression model. similarly, in an effort to maintain clinical relevance and overcome dilutional effects, some continuous variables were converted to categorical alternatives (e.g., oxygen saturation less than 95%, based on convention), recognizing that doing so could sacrifice information. 51 although the decision was made not to pair cases and controls temporally, the acceleration and deceleration of the pandemic wave in new york city still likely influenced the acuity of patients presenting over time. in summary, these data suggest an opportunity for risk stratification prior to discharge of suspected covid-19 patients. the period of time examined is unparalleled and, in new york city, unlikely to reflect the acuity, volume, and management strategies to follow. successful implementation of more rapid and reliable testing may one day allow for definitive diagnosis in the ed, such that further clarification of these risks will be made possible. but, in this unprecedented moment, the findings detailed here may offer some guidance to those clinicians still facing these unknowns from the frontline. figure 1 . ed volume by disposition during the covid-19 pandemic, with the stacked area plot (leftward axis) demonstrating trends in discharges and admissions over time with suspicion (dotted and striped, respectively) and without suspicion (grey and dark grey, respectively) for covid-19. overlying is a line graph (rightward axis) depicting those publicly available confirmed daily cases in new york city, as of may 14th. figure 2 . consort flow diagram demonstrating derivation of the study group of those suspected covid-19 ed discharges returning within 72 hours for hospital admission, the control group of those suspected covid-19 discharges not returning within 72 hours for admission, and the nested control group for direct comparison of various clinical features of the first hospital encounter. excluded were 19 ed discharges with discrepant visit timelines that were either erroneously duplicated or should have been treated as continuous encounters. table 1 . characteristics of 139 patients returning after discharge to one of five new york city eds within 72 hours for admission. *fisher's exact test was used for determination of p-value. **racial breakdown limited by institutional data collection. table 2 . additional clinical characteristics of patients returning for hospital admission within 72-hours of discharge. *fisher's exact test was used for determination of p-value. **by definition, all members of the study group returned to the ed within 72 hours of discharge, and all of these patients were admitted on that subsequent encounter. the control cohort, however, includes some patients who returned to the ed within 72 hours, although none were admitted. table 3 . multivariable logistic regression analysis of 72-hour return admission for suspected covid-19 discharges, demonstrating regression coefficients, odds ratios, and 95% confidence intervals of odds ratios. * included were those variables with p<0.05 in univariate analysis. 1 result was removed due to missing data. case-fatality estimates for covid-19 calculated by using a lag time for fatality. emerg infect dis intubation and ventilation amid the covid-19 outbreak: wuhan's experience nowcasting and forecasting the potential domestic and international spread of the 2019-ncov outbreak originating in wuhan, china: a modelling study data-based analysis, modelling and forecasting of the covid-19 outbreak covid-19 and italy: what next? lancet estimates of the severity of coronavirus disease 2019: a model-based analysis allocating scarce resources in disasters: emergency department principles emergency departments and the covid-19 pandemic: making the most of limited resources facing covid-19 in italy -ethics, logistics, and therapeutics on the epidemic's front line fair allocation of scarce medical resources in the time of covid-19 challenges in laboratory diagnosis of the novel coronavirus sars-cov-2 clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study clinical characteristics of refractory covid-19 pneumonia in wuhan, china comorbidity and its impact on 1590 patients with covid-19 in china: a nationwide analysis united states covid-19 cases: reported to the cdc since clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china frequency and distribution of chest radiographic findings in covid-19 positive patients portable chest x-ray in coronavirus disease-19 (covid-19): a pictorial review risk factors for 72-hour admission to the ed risk factors and prognostic predictors of unexpected intensive care unit admission within 3 days after ed discharge predictors of admission in adult unscheduled return visits to the emergency department characteristics and determinants of high-risk unscheduled return visits to the emergency department the impact of copd and smoking history on the severity of covid-19: a systemic review and meta-analysis association between hypoxemia and mortality in patients with covid-19 single breath counting in the assessment of pulmonary function assessment of respiratory distress by the roth score distance and oxygen desaturation during the 6-min walk test as predictors of long-term mortality in patients with copd six-minute walk test: clinical role, technique, coding, and reimbursement clinical characteristics of covid-19 patients with digestive symptoms in hubei, china: a descriptive, cross-sectional, multicenter study epidemiological, clinical and virological characteristics of 74 cases of coronavirusinfected disease 2019 (covid-19) with gastrointestinal symptoms obesity and its implications for covid-19 mortality kidney disease is associated with in-hospital death of patients with covid-19 thrombocytopenia is associated with severe coronavirus disease 2019 (covid-19) infections: a meta-analysis neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with covid-19 evaluating unscheduled readmission to emergency department in the early period factors associated with short-term bounce-back admissions after emergency department discharge seventy-two-hour returns may not be a good indicator of safety in the emergency department: a national study patient returns to the emergency department: the time-to-return curve return visits to the emergency department emergency department revisits bounces": an analysis of short-term return visits to a public hospital emergency department the association between limited english proficiency and unplanned emergency department revisit within 72 hours 2019-ncov persons under investigation team; 2019-cov persons under investigation team. persons evaluated for 2019 novel coronavirus -united states epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study bouncing back elsewhere: multilevel analysis of return visits to the same or a different hospital after initial emergency department presentation common pitfalls in statistical analysis: logistic regression discharge in pandemic: suspected covid-19 patients returning to the emergency department within 72 hours for admission authors: colton margus: conceptualization, project administration, investigation, methodology, software, formal analysis, data curation methodology, investigation, writing-original draft nathan m peck: methodology, writing-reviewing and editing bess storch: writing-reviewing and editing ka ming ngai: writing-reviewing and editing hsi en ho: supervision, conceptualization, data curation, writing-reviewing and editing trent she: supervision, conceptualization, project administration, investigation, methodology, writing-reviewing and editing we thank wei zhao, m.d., m.sc. for methodological guidance, which greatly improved the manuscript.  the covid-19 pandemic wave in new york city led to an unprecedented challenge for emergency departments (eds) aiming to discharge without the ability to accurately diagnose those patients suspected of covid-19  discharged ed patients returning within 72 hours were more often admitted if suspected of covid-19 than those that were not  suspected covid-19 patients discharged from the ed were more likely to be admitted within 72 hours if they were older, male, or with a history of obstructive lung disease or diabetes  fever, tachycardia, dyspnea, gastrointestinal symptoms, x-ray abnormalities, and decreased platelets and lymphocytes were all associated with 72-hour return admission  patients suspected of covid-19 returning within 72 hours for admission suffered significant morbidity and mortality, with most requiring oxygen supplementation key: cord-322778-a411t2wg authors: skalidis, ioannis; nguyen, vinh kim; bothorel, hugo; poli, lauriane; da costa, rui ribeiro; younossian, alain bigin; petriccioli, nicole; kherad, omar title: unenhanced computed tomography (ct) utility for triage at the emergency department during covid-19 pandemic date: 2020-07-28 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.058 sha: doc_id: 322778 cord_uid: a411t2wg background: unenhanced chest computed tomography (ct) can assist in the diagnosis and classification of coronavirus disease 2019 (covid-19), complementing to the reverse-transcription polymerase chain reaction (rt-pcr) tests; the performance of which has yet to be validated in emergency department (ed) setting. the study sought to evaluate the diagnostic performance of chest ct in the diagnosis and management of covid-19 in ed. methods: this retrospective single-center study included 155 patients in ed who underwent both rt-pcr and chest ct for suspected covid-19 from march 1st to april 1st, 2020. the clinical information, ct images and laboratory reports were reviewed and the performance of ct was assessed, using the rt-pcr as standard reference. moreover, an adjudication committee retrospectively rated the probability of covid-19 before and after the ct calculating the net reclassification improvement (nri). their final diagnosis was considered as reference. the proportion of patients with negative rt-pcr test that was directed to the referent hospital based on positive ct findings was also assessed. results: among 155 patients, 42% had positive rt-pcr results, and 46% had positive ct findings. chest ct showed a sensitivity of 84.6%, a specificity of 80.0% and a diagnostic accuracy of 81.9% in suggesting covid-19 with rt-pcr as reference. concurrently, corresponding values of 89.4%, 84.3% and 86.5% were retrieved with the adjudication committee diagnosis as reference. for the subgroup of patients with age > 65, specificity and sensitivity were 50% and 80.8%, respectively. in patients with negative rt-pcr results, 20% (18/90) had positive chest ct finding and 22% (4/18) of those were eventually considered as covid-19 positive according to the adjudication committee. after ct, the estimated probability of covid-19 changed in 10/104 (11%) patients with available data: 4 (4%) were downgraded, 6 (6%) upgraded. the nri was 1.92% (nri event −2.08% + nri non-event 5.36%). no patient with negative rt-pcr but positive ct was eventually directed to hospital. conclusion: chest ct showed promising sensitivity for diagnosing covid-19 across all patients' subgroups. however, ct did not modify the estimated probability of covid-19 infection in a substantial proportion of patients and its utility as an emergency department triage tool warrants further analyses. j o u r n a l p r e -p r o o f according to the adjudication committee. after ct, the estimated probability of covid-19 changed in 10/104 (11%) patients with available data: 4 (4%) were downgraded, 6 (6%) upgraded. the nri was 1.92% (nri event -2.08% + nri non-event 5.36%). no patient with negative rt-pcr but positive ct was eventually directed to hospital. chest ct showed promising sensitivity for diagnosing covid-19 across all patients' subgroups. however, ct did not modify the estimated probability of covid-19 infection in a substantial proportion of patients and its utility as an emergency department triage tool warrants further analyses. during the current covid-19 pandemic, triage is an essential process in most emergency departments (ed) owing to overcrowding and the impossibility of taking care of every patient immediately. early diagnosis of covid-19 is key to improving outcomes in the absence of specific therapeutic drugs or vaccines. currently reverse-transcription polymerase chain reaction (rt-pcr) is the gold standard for diagnosing covid-19. the clinical utility of rt-pcr is limited however by global shortages of rt-pcr viral testing reagents, the limited number of laboratories that can meet rigorous quality standards, the length of time required for results to become available, and a clinically significant false negative rate. in parallel, there is a growing number of publications describing ct j o u r n a l p r e -p r o o f appearance in the setting of known or suspected covid-19 infection (1) (2) (3) (4) . some studies also suggest that chest computed tomography (ct) in particular may be positive in the setting of a negative rt-pcr test (5) (6) (7) (8) . as a result there is growing interest in the role and appropriateness of ct in the screening, diagnosis and management of patients with suspected or known covid-19 infection(1, 9) . ct based strategy for patients suspected for covid-19 infection could improve sensitivity and specificity but has never been validated in ed setting. data supporting such a strategy are lacking and current clinical merit further analysis. the use of a ct based strategy in the emergency department setting may allow determination of the level of priority of a given patient and facilitate direction into covid positive cohorts from emergency departments to referral hospitals. we therefore conducted this retrospective study to evaluate the diagnostic performance of ct in patients presenting to ed with covid-19 suspicion compared with both rt-pcr, which is currently used as a gold standard, and a clinical adjudication committee decision. from march 1 st to april 1 st 2020, patients with suspected covid-19 infection who underwent both rt-pcr test and unenhanced ct screening at the emergency department (ed) of la tour hospital were included. this hospital is a secondary academically affiliated hospital and the 2nd largest ed in the canton of geneva, switzerland (23,343 visits in 2017). patients who were included were all symptomatic (fever and/or dyspnea and/or cough) and if they required a hospital admission they were directed to the referent tertiary center, the geneva university hospital (hug) (72,921 patients admitted in 2018) in accordance to the local policy recommendation to maintain and cohort patients with covid-19 in a single referral center in each region. as in many centers, la tour hospital and hug developed their own scale for hospital triage and admission decision, based mainly on clinical parameters. (table 1) . pregnant women and patients under the age of 18 were excluded. following the experience in china, la tour hospital integrated a modified version of the national early warning score (news) with age ≥ 65 years added as an independent risk factor based on recent reports (10) . based on this score, patient with score >4 must all be transferred to referent hospital for monitoring. hospital admission could also be considered for patients with score 1-4. (table 1 ) final decision was left to the discretion of attending physicians. in all patients, the delay between the two tests was less than 24hrs (range 4h-24h). the rt-pcr results were extracted from the patients' electronic medical records in our hospital information system. specimens' collection was performed by the same nurse study. nasopharyngeal swab was used and send to the -centre national de référence pour les infections virales émergentes‖ (crive) at hug. the rt-pcr assays were performed by using cobas® 6800 sars-cov-2 system from roche, f. hoffmann-la roche ltd: roche's cobas sars-cov-2 test to detect novel coronavirus received fda emergency use authorization ltd. ct examinations were performed using a 64 slices mdct scanner (somatom definition; as siemens healthineers, forchheim, germany). patients were scanned in the supine position, during breath hold and with feet towards the gantry. the main scanning parameters j o u r n a l p r e -p r o o f were as follow: tube voltage = 100 kvp, automatic tube current modulation (mean 50 mas), pitch = 1.1 mm, matrix = 512 × 512, slice thickness = 10 mm, field of view = 350 mm × 350 mm. for each patient, two reconstructions were performed (utilizing the small 1 mm and large 3 mm thick images) and stored in the pacs system. no premedication with betablockers or nitrates was added before ldct acquisition. all patients were examined with the same standardized examination protocol. ct were unenhanced with relatively low dose (2 to 2.5 msv). all images were reviewed independently by two experienced specialists with more than 10 years of experience in interpreting chest ct imaging (first by a radiologist and then by a pulmonologist). both were blinded to rt-pcr results but were aware of the epidemiological characteristics and clinical symptoms of the patients. ct findings included ground glass opacity (ggo), consolidation, air bronchogram and nodular opacities. ggo was defined as hazy areas of increased opacity or attenuation with visible underlying vessels. each specialist classified the abnormal ct according to ggo distribution of the affected lung parenchyma graded on a 3-point scale: 1=light <30%, 2=moderate 30-60%, 3= severe >60%. finally, the results of the classification were merged by consensus and the specialists classified the ct on positive or negative for covid-19. the adjudication committee was composed of 5 board-certified specialists in respiratory diseases and internal medicine. all were senior attending physicians with expertise in caring for patients with respiratory tract infections. after the completion of the study, the adjudication committee, blinded to the rt-pcr results, retrospectively reviewed the ed admission charts of all patients and graded the probability of covid-19 by integrating data from several parts of the chart: the history section, the results of the clinical examination and the laboratory tests. they assess these probabilities independently, blinded to each other's assessments. first, each expert gave an individual opinion of the probability of the patient having covid-19 on a three-point likert scale (low, intermediate, high); second, each expert re-examined the cases where the committee had been in disagreement, in full knowledge of the other experts' first decisions. finally, in plenary session, the adjudication committee made consensus decisions on cases that remained unresolved after the first two phases. adjudication committee was then informed of the ct interpretation and made a new evaluation of the probability of covid-19 by incorporating the results of the ct and the radiologist's interpretation, repeating the 3-phases process. after integrating the results of rt-pcr (integrating serial analyses if available) and the clinical follow-up in the referral hospital, their final consensus decision was considered as the reference diagnosis for covid-19 infection. the study primary endpoints were the test diagnostic characteristics; specifically, sensitivity, specificity, positive and negative predictive values of ct first in comparison to rt-pcr as gold standard and, second, to the final adjudication committee decision. for patients with negative rt-pcr tests but positive ct results, follow-up rt-pcr analyses and/or ct images were tracked to further confirm the imaging diagnosis if available. secondary endpoints were the proportion of patients whose probability of covid-19 changed (upgraded or downgraded) before and after ct and the proportion of modified j o u r n a l p r e -p r o o f diagnoses which matched the reference diagnosis, the proportion of patients for whom positive ct results but negative rt-pcr modified the patient's direction (hospital admission or outpatient follow-up); the proportion of patient for whom positive ct results modified the patient's direction according news score 1-4 whilst awaiting the rt-pcr results. continuous variables were expressed as mean ± sd, and discrete variables were expressed as absolute numbers and percentages. sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv), accuracy of chest ct imaging were calculated, using rt-pcr as the gold standard. similar tests were performed with final adjudication committee decision as standard of reference. a 95% confidence interval was provided by the wilson score method. a p value < 0.05 was considered statistically significant. the performance of chest ct for identifying covid-19 in different age groups (<60 years and ≥ 60 years) and by gender was compared by the chi-square test. the estimated probabilities of covid-19 before and after the ct were compared, and the proportion of modified diagnoses (95% ci) was calculated. to assess whether ct helped clinicians to better reclassify patients in agreement with reference diagnoses, we calculated the net reclassification improvement (nri based on the findings of ai et al. (5) who found a ct sensitivity of 97%, specificity of 25% and a prevalence of covid-19 infection of 59% in a population with suspicion of infection (rt-pcr testing), the minimum sample size needed to evaluate the ct diagnostic performance with 80% power and confidence interval width of 14% is: 60 patients for sensitivity evaluation and 130 patients for specificity evaluation. in order to have sufficient cases to evaluate both sensitivity and specificity, our sample size needed would therefore be 130 patients. approval for the retrospective analysis of the patients with covid-19 suspicion was obtained from the swiss ethics commission (commission cantonale d'éthique de la recherche ccer2020-00687) and written informed consent was waived. from march 1 st to april 1 st 2020, a total of 155 patients that underwent both rt-pcr and chest ct were included in our retrospective study analysis. the mean age was 60.0 ± 18.46 years, with 48% men. of 155 patients, 42% had positive and 58% had negative rt-pcr results. ( according to the adjudication committee, the initial probability of covid-19 was high in 49 table 4 ]. more than 57% of patients with intermediate pre-ldct probability had their probability changed after ct. the changes in clinician's probability subsequently matched the reference diagnoses in 66.6% of modifications (4/6) and in 80.8% of all patients (84/104). the absolute number of patients correctly reclassified according to the diagnosis of adjudication committee is -1 patient among those with covid-19, and +3 among those without covid-19. overall, the absolute number of patients correctly reclassified is thus +2 patients, corresponding to 1.92% of all patients in our sample. the nri was 1.92% (nri event -2.08% + nri non-event 5.36%). [ table 5 ] follow-up information was available in 111 patients. 54/111 (49%) were directed to the referral hospital and 57/111 (51%) were followed in ambulatory setting as outpatients. 53 had news score >4, 25 had news score between 1-4 and 33 had news score=0. ct results modified the direction of 16 patients awaiting results of rt-pcr (which could take up to 24 hours). ten patients with news score between 1-4 were not referred because the ct revealed light ggo lesions (<30%). six patients with news score between 1-4 were j o u r n a l p r e -p r o o f admitted to the referral hospital because of moderate to severe ggo lesions on ct scan. of note, 3 patients with news score 1-4 and abnormal ct scan transferred to the referent hospital were denied admission because their hospital triage scale did not integrate the chest ct results. among patients with positive chest ct but negative rt-pcr, none was eventually admitted to the referral hospital. this study assessed a ct based triage strategy in a swiss ed setting during the covid-19 pandemic. the strength of this study is to combine clinical probability and ct to determine whether the results would change likelihood of disease process. the diagnostic performance of ct for covid-19 infection is promising, reflecting previous data from china (5) . with rt-pcr results as gold standard in 155 patients, the sensitivity, specificity, accuracy of chest ct in indicating covid-19 infection were 84.6%, 80.0% and 75.3%, respectively. the positive predictive value and negative predictive value were 75.3% and 87.8%, respectively. in our study, the positive rate of rt-pcr assay for throat swab samples was 46% which similar than previous report (30 -60%)(5). one of the main concerns with the covid-19 pandemic is the low to very low sensitivity of rt-pcr (50-83%) (5, 11) . patients with negative rt-pcr but ct scan suggestive of covid-19 represents either a false negative rt-pcr or a false positive ct scan. to overcome this issue, those patients with discordant findings between negative rt-pcr and positive ct were tracked retrospectively in our study by an adjudication committee: based on the analysis of clinical symptoms, ct features and serial rt-pcr if available, 4/18 patients with discordant results were reclassified as clinically diagnosed cases of covid-19. therefore, with the adjudication committee decision as diagnostic reference, the diagnostic performance of ct scan was even better: sensitivity of 89.4%, specificity of 84.3%, and overall accuracy of 86.5%. the negative predictive value was 91.4% and positive predictive value was 75.0% non-pharmaceutical interventions are widely implemented for pandemic mitigation (i.e. delaying and flattening the peak) (12) . among these different measures massive testing in symptomatic patients and contact tracing followed by isolation are supported by who. according to current diagnostic criteria, viral nucleic acid test by rt-pcr assay plays a vital role in determining hospitalization and isolation for individual patients. however, its lack of sensitivity and relatively long time to obtaining test results were detrimental to the control of the disease epidemic. furthermore, several countries, including switzerland, faced frequent shortages of rt-pcr tests. switzerland is among the countries with the highest number of covid-19 cases per capita in the world, but testing efforts are currently not detecting all infected people, including some with clinical disease compatible with covid-19 (13) . in this context, a strategy using ct-scanning alongside rt pct for covid-19 diagnosis may improve the effectiveness of screening in symptomatic patients. it may also improve timeliness of diagnosis and offer a solution when rt-pcr tests are unavailable. globally, specificity of ct scan was higher in our study than previously described(5) but remains less than optimal as other viruses and non -infectious pathologies can mimic ggo ct lesions (14) . in our study, 14 patients had positive ct but negative rt-pcr and were considered as potentially falsely positive by the adjudication committee. furthermore, ct did not appear to add diagnostic value as positive results depend on pre-test probability and are more likely when the prior probability is low. considering our ct specificity, the ppv in our cohort was 50% if pretest probability was low. to the best of our knowledge, our study is the first assessing the utility of ct scans that integrates the pre-test probability. ct results j o u r n a l p r e -p r o o f changed the probability of a diagnosis of covid-19 in a small proportion of patients (9.6%), upgrading the probability in 3.8% and downgrading it in 5.8%. the absolute net reclassification index was 1.92% and nri non-event was not superior to nri event, meaning that ct doesn't help to exclude a diagnosis of covid-19. furthermore, the results of ct scan did not modify the direction of patients with suspected covid-19 in the majority of the cases: only 16 patients of 155 had their direction changed after the results of ct scan. ten patients (news score 1-4) were maintained in ambulatory care because the ct revealed only light ggo lesions (<30%). conversely, 6 patients without absolute admission criteria (news score <5) were admitted to referent hospital because of moderate to severe ggo lesion on ct scan. all of them had finally a positive rt-pcr. of note, 3 of them were refused by the referent hospital and were re-transferred because of absence of clinical admission criteria. ct findings do not seem being associated with intensive care unit (icu) admission (15) and their prognostic value for assessing mortality must be confirmed (16) . overall, these results confirmed that when covid-19 is suspected, patients should be isolated pending confirmation with (multiple) rt-pcr tests, or until quarantine has lapsed. if hospital admission criteria are present, patients should be transferred to the referral hospitals. the results of a ct scan did not change this in our study. furthermore, using ct to diagnose covid-19 patients is logistically challenging and can overwhelm available resources. the american college of radiology (acr) recently recommended against ct for screening tests: -..ct should be used sparingly and reserved for hospitalized, symptomatic patients with specific clinical indications for ct‖(1). our study presents the inherent limitations of any retrospective study: first, it included only individuals who received both rt-pcr and ct. in absence of specific guidelines or protocols dictating who must underwent imaging, ct prescription was left to the discretion of attending physician with a risk of selection bias that may skew the perceived performance of ct. it is reflected by the overall high positivity rate of rt-pcr in our population. beyond this selection bias, switzerland is among the countries with the highest number of covid-19 cases per capita, limiting the generalizability of the data in low incidence area. second, even if data for performance analyses were complete, data on follow-up were missing in 44 patients and were excluded, exposing to biased estimates. furthermore, the time of onset of symptoms was poorly identified limiting the assessment of the evolution of covid-19 pneumonia on ct, and rt-pcr positivity (7) . ct abnormalities might predate rt-pcr positivity in symptomatic patients and in those without symptoms who subsequently test positive by rt-pcr. chest x-ray performance was not assessed in this study as this test was not performed for safety reasons: even with proper cleaning protocols, as involved health-care workers technician could become vectors of infection to other vulnerable patients who require imaging. this was less an issue as a ct scan was dedicated to covid-19 and performed in closed-circuit with standardized cleaning delay. finally, as the predominant pattern seen in covid-19 pneumonia is ggo, detecting covid-19 with use of chest x-ray-where this type of abnormality is often undetectable, particularly in patients with few symptoms or low severity-will be limited. j o u r n a l p r e -p r o o f ct utility remains uncertain for the diagnosis and management of covid-19. its diagnostic performance seems promising with good sensitivity across all patient subgroups. however, ct did not modify the estimated probability of covid-19 infection in a substantial proportion of patients and its utility as a triage tool is debatable. its prognostic value could be further enhanced if it was able to define early radiological abnormalities or patterns that predict a poor outcome such as icu admission. more research is needed into the correlation of ct findings with clinical severity and progression, the predictive value of baseline ct or temporal changes for disease outcome, and the sequelae of acute lung injury induced by covid-19. meanwhile, we urge caution using systematically ct, keeping in mind that, now more than never, protecting limited resources is critical. all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 helsinki declaration and its later amendments or comparable ethical standards. necessity of informed consent for patient data utilizing was waived due to the current pandemic situation. j o u r n a l p r e -p r o o f table 3 . diagnostic performance of ct with rt-pcr and with adjudication committee as references table 4 . clinician's estimates of probability of covid-19 before and after ct statements/recommendations-for-chest-radiography-and-ct-for-suspected-covid19-infection the clinical and chest ct features associated with severe and critical covid-19 pneumonia ct features of coronavirus disease 2019 (covid-19) pneumonia in 62 patients in wuhan, china novel coronavirus (2019-ncov) pneumonia correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases chest ct for typical 2019-ncov pneumonia: relationship to negative rt-pcr testing radiological findings from 81 patients with covid-19 pneumonia in wuhan, china: a descriptive study sensitivity of chest ct for covid-19: comparison to rt-pcr the role of ct in case ascertainment and management of covid-19 pneumonia in the uk: insights from highincidence regions novel coronavirus infection during the 2019-2020 epidemic: preparing intensive care units-the experience in sichuan province, china detection of sars-cov-2 in different types of clinical specimens nonpharmaceutical interventions implemented by us cities during the 1918-1919 influenza pandemic covid-19 epidemic in switzerland: on the importance of testing, contact tracing and isolation a role for ct in covid-19? what data really tell us so far clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in wuhan the authors have no disclosure. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. the authors declared no potential conflicts of interests associated with this study. key: cord-322297-euqmv6rw authors: kim, sung hyun; shin, sang do; song, kyoung jun; ro, young sun; kong, so yeon; kim, jeongeun; ko, seo young; lee, sun young title: association between ambient pm(2.5) and emergency department visits for psychiatric emergency diseases() date: 2018-11-24 journal: am j emerg med doi: 10.1016/j.ajem.2018.11.034 sha: doc_id: 322297 cord_uid: euqmv6rw background: whether or not short-term exposure to particulate matter <2.5 μm in diameter (pm(2.5)) increases the risk of psychiatric emergency diseases is unclear. methods: the study was performed in a metropolis from january 2015 to december 2016. the exposure was pm(2.5), and the confounders were weather (temperature and humidity) and other pollutants (pm(10), so(2), co, o(3), and no(2)). the outcomes were emergency department (ed) visits with psychiatric disease codes (f00-f99 in icd10 codes). general additive models were used for the statistical analysis to calculate the adjusted relative risks (arrs) and 95% confidence intervals (95% cis) for the daily number of ed visits with a lag of 1 to 3 days following a 10 μg/m(3) increase in pm(2.5). results: during the study period, a total of 67,561 ed visits for psychiatric diseases were identified and tested for association with pm(2.5). daily ed visits for all psychiatric diseases were not associated with pm(2.5) in the model that was not adjusted for other pollutants. the arr (95% ci) in the model adjusted for so(2) was 1.011 (1.002–1.021) by 10 μg/m(3) of pm(2.5) on lag 1 for all psychiatric diseases (f00-f99). the arr (95% ci) in the model adjusted for o(3) was 1.015 (1.003–1.029) by 10 μg/m(3) of pm(2.5) on lag 1 for f40-f49 (neurotic, stress-related and somatoform disorders). conclusion: an increase in pm(2.5) showed a significant association with an increase in ed visits for all psychiatric diseases (f00-f99) and for neurotic, stress-related and somatoform disorders (f40-f49) on lag day 1. psychiatric diseases account for approximately 6.2% of the global disease burden measured by disability adjusted life years (dalys) and affected n400 million people globally in 2015 [1] . approximately 4.3 million people visited emergency department for emergency psychiatric diseases in the usa, which accounted for 21 visits per 1000 adults in 2000 [2] . the risk factors must be identified to prevent acute exacerbation of psychiatric diseases. pm 2.5 , which is the abbreviation for particulate matter 2.5 μm or less in diameter, is one of the most important potential environmental hazards for health conditions and mortality. ambient pm 2.5 exposure has been found to be a leading cause of death and disability worldwide [3] . a 10 μg/m 3 increase in pm 2.5 corresponds to a 0.68% increase in cardiovascular mortality [4] . short-term exposure to pm 2.5 induces respiratory hospital admissions [5, 6] , increases total cerebrovascular disease mortality [7] , and even aggravates already diagnosed parkinson's disease [8] . although studies have investigated the relationship between emergency department visits for depression and ambient pm 2.5 exposure [9] [10] [11] [12] , studies on other emergency psychiatric diseases and pm 2.5 are rare. air pollutants may cause activation of inflammatory processes, the immune system, oxidative stress, and alterations in cerebral neurotransmitter concentrations [13] [14] [15] , which can lead to mental or behavioral alterations. therefore, an increase in pm 2.5 may exacerbate emergency psychiatric diseases. the purpose of this study is to determine the association between ambient pm 2.5 exposure and visits to the emergency department (ed) for emergency psychiatric diseases. this study is a cross-sectional observational study to evaluate the association between the number of patients visiting the ed for psychiatric diseases and the pm 2.5 concentration in seoul, korea. according to the national statistical office, the population of seoul is 10 million people, which represents one-fifth of the korean population. seoul is one of the most highly populated cities in the world, with a population density of 16,492/km 2 reported in 2017. seoul has an area of 605 km 2 and consists of 25 health and administrative districts. according to the korea meteorological administration, the average annual temperature of seoul is 12.5°c (54.5°f), but the temperature varies greatly depending on the season, with an average temperature in august of 25 according to statistics from the ministry of health and welfare, there are 51 emergency departments in seoul, which the national government has classified into three groups. these departments include 4 level 1 departments with a mission to provide a full range of emergency care services and disaster medical services that are staffed by emergency physicians 24 h per day and 7 days per week, 27 level 2 emergency departments where emergency physicians are on standby 24 h per day 365 days per year to provide general comprehensive emergency care services, and 20 level 3 emergency departments staffed by general physicians to provide general emergency care services. a total of 610 emergency medicine specialists, 217 residents, and 1290 nurses worked at the emergency departments in seoul in 2016. a total of 1.8 million citizens visit the emergency departments annually in seoul, including more than thirty thousand visits for psychiatric emergency diseases per year. we used four data sources for this study. the first data set for the seoul population was collected from the national statistical office. the data set includes the population size, age distribution, gender distribution, and residence on a nationwide scale for policy making every year using family registry documents. the second set of data on emergency department visits from the 51 hospitals in seoul was obtained from the national emergency department information system (nedis) of the national emergency medical center (nemc). the nemc is the central headquarters of the emergency care system for quality assurance, evaluation, and emergency care program grants. the nemc has collected nedis data since 2004 from 16 level 1 eds; the nemc collected data from 408 of the 413 emergency departments in the country in 2016 and from 403 emergency departments out of 420 in 2015. all 51 emergency departments in seoul were included in both years. the nedis data include sex, age, when the event occurred, the patient's main symptom, the diagnosis, which emergency department the patient visited, and the address of the patient. the data are verified by the automatic system; if modification or reexamination is necessary, each emergency department revises the data [16] . the third set of meteorological data, including the daily mean temperature, relative humidity, and air pressure, was obtained from the korean meteorological administration. the administration was established in 1949 and has collected meteorological data since that time. in seoul, 35 automatic weather systems (awss) measure weather information every minute to inform citizens of weather situations and collect data for research. [17] the fourth data source provided air pollutant monitoring data obtained from the korean national institute of environmental research. this data source provides the average concentrations of air pollutants, including pm 2.5 , pm 10 , carbon oxide (co), nitric dioxide (no 2 ), sulfur dioxide (so 2 ), and ozone (o 3 ), every hour using monitoring stations. the institute collects data from 40 monitoring stations in seoul to provide information to citizens and researchers as a pollution alarm. [18] the population aged 15 years and older in 2015 and 2016 was included in this study. we excluded children (b15 years old) and individuals who were not registered as residents at the district office, such as temporary visiting foreigners and travelers. we used the daily average concentration of the hourly pm 2.5 for each district as the main exposure. the daily average concentration was provided by the data source. the variables included the daily mean temperature, relative humidity, air pressure, age, gender, day of the week, season, and patient addresses. the middle east respiratory syndrome (mers) outbreak occurred over a two-month period in 2015 when several eds were closed, and the number of ed visits decreased. therefore, the mers outbreak period was added as a variable. the pm 2.5 concentration was measured using the beta-ray absorption method, the pm 10 concentration was measured using beta-ray absorption in μg/m 3 , co was measured with the non-dispersive infrared method, no 2 was measured using chemiluminescence, so 2 with measured with ultraviolet fluorescence, and o 3 was measured using ultraviolet photometry. the outcome was the daily number of people who visited the emergency departments in seoul from 2015 to 2016 with a diagnostic code for psychiatric diseases (international classification of disease-1oth version, mental and behavioral disease, f00-f99, including f00-f09 (organic, including symptomatic, mental disorders), f10-f19 (mental and behavioral disorders due to psychoactive substance use), f20-f29 (schizophrenia, schizotypal and delusional disorders), f30-f39 (mood [affective] disorders), f40-f48 (neurotic, stress-related and somatoform disorders), f50-f59 (behavioral syndromes associated with physiological disturbances and physical factors), f60-f69 (disorders of adult personality and behavior), f70-f79 (mental retardation), f80-f89 (disorders of psychological development), f90-f98 (behavioral and emotional disorders with onset usually occurring in childhood and adolescence), and f99-f99 (unspecified mental disorder)). the diagnostic codes for ed care were inputted by the emergency physicians when the patients were discharged to home, transferred to another hospital, or admitted to a ward. in addition to the ed diagnosis, the duty physicians inputted the diagnostic codes into the electronic medical records when the patients were discharged after admission. a maximum of 20 diagnostics codes can be uploaded to the nedis server. the nedis diagnostic codes are used for the national emergency department evaluation program, which is performed annually by the ministry of health and welfare as a source of diagnostic codes, and are also used for the reimbursement program of the national health insurance corporation. therefore, most hospitals rigorously manage the diagnostic codes to ensure reliability and validity. demographic information was collected, including information for patients with emergency psychiatric diseases (age, gender, season, month, day of the week, disease category, mers period, and district), weather (daily temperature, humidity, and pressure), and pollutants (pm 10 , co, no 2 , so 2 , and o 3 ). we determined the correlations between the pollutants using the r package version 3.2.3 (r foundation for statistical computing, vienna, austria). a time-series analysis using a generalized additive model (gam) was used to calculate adjusted relative risks (arrs) with 95% confidence intervals (95% cis), because most epidemiological air pollution studies (cited in the second paragraph of the article) used this approach. the model was controlled for daily mean temperature, relative humidity, and mean air pressure, which were treated as continuous variables, as well as for the day of the week. the basic model is as follows: where y is the daily number of emergency department visits for psychiatric diseases, x1, …, xp are covariates, s i () is a nonparametric smoother, and pm 2.5 is the mean value for the corresponding day. a total of 4 degrees of freedom were selected to smooth the time trends. we examined the concentrations of the individual lag days 1 through 3 (lag 1 represents the pm 2.5 level one day prior to the emergency room visit, lag 2 is the previous day, and so on). we tested the association between pm 2.5 and all emergency psychiatric diseases and subgroups of emergency psychiatric diseases (f20 to f50) to calculate the arrs (95% cis) using the gam model described above. all statistical analyses for the gam data processing were performed using the sas software, version 9.4 (sas institute inc., cary, nc, usa). the study population over 15 years of age in seoul included 8,734,321 citizens in 2015 and 8,675,108 citizens in 2016. in total, 67,561 patients with psychiatric emergencies (33,041 in 2015 and 34,520 in 2016) were analyzed (fig. 1) . table 1 shows the study population and the numbers of ed visits. a total of 67,561 emergency department visits were identified in seoul from january 2015 to december 2016 (731 days). emergency department visits for icd codes f10-f19 (mental and behavioral disorders due to psychoactive substance use) represented the largest subgroup, because alcohol abuse was included. generally, the total ed visits were higher in women than in men, although this trend was not observed in some subgroups. more visits occurred in the summer than in the winter. table 2 summarizes the key variables. the mean ed (standard deviation) visits for psychiatric diseases and the mean pm 2.5 level was 92 (12) and 24.8 (15. 2) μg/m 3 . on 121 days corresponding to the 17th percentile, the daily mean pm 2.5 was below 15 μg/m 3 , which was a level classified as "good" by the korean meteorological administration. the daily mean pm 2.5 was above 50 μg/m 3 , which was a "bad" level, on 11 days. fig. 2 shows the number of ed visits for psychiatric diseases and the daily mean pm 2.5 concentrations for each date. fig. 3 shows correlations among the pollutants and ed visits. the ed visits for psychiatric disease were not significantly correlated with the daily pm 2.5 concentrations (p = 0.149). table 3 shows the associations between pollutants (so 3 , co, o 3 , and no 2 ) and ed visits for psychiatric diseases in the gam models. so 2 was significantly associated with decreased ed visits for all psychiatric diseases on lag day 1 (0.991, 0982-0.999). co was also significantly associated with a decrease in ed visit due to f20-f29 (0.966, 0.944-0.989), whereas o 3 was associated with increased ed visits (1.039, 1.001-1.079). codes f40-f49 were significantly increased on lag day 1 by an increase in no 2 (1.015, 1.001-1.031). table 4 shows the associations between pm 2.5 and ed visits for psychiatric diseases. ed visits for all psychiatric diseases were not associated with pm 2.5 in the analyses that were not adjusted for the other pollutants. the arr (95% ci) in the model adjusted for so 2 was 1.011 (1.002-1.021) for a 10 μg/m 3 increment of pm 2.5 on lag day 1 for all psychiatric diseases (f00-f99). the arr (95% ci) in the model adjusted for o 3 was 1.015 (1.003-1.029) for a 10 μg/m 3 increment of pm 2.5 on lag day 1 for f40-f49 (neurotic, stress-related and somatoform disorders). the other models did not show any significant associations between pm 2.5 and ed visits due to psychiatric diseases. we found a significant association between the pm 2.5 concentration and emergency department visits for psychiatric diseases on lag 1 day in the adjusted models. ed visits due to all types of psychiatric diseases following an increase in pm 2.5 were increased on lag day 1 after fig. 1 . study population. ed, emergency department. adjustment for so 2 . ed visits with codes f40-f49 were also increased on lag day 1 by an increase in pm 2.5 after adjustment for o 3 . our study did not show consistent effects due to increases in pollutants, as reported in previous studies. one possible reason is the relatively low pm 2.5 levels in seoul in this study setting compared with other studies. the mean (standard deviation) of pm 2.5 was 24.8 (15.2) , and only 31 days had pm 2.5 concentrations n50 μg/m 3 . among the 40 air pollutant monitoring stations, 25 are located in each district of seoul at community service centers or other public buildings, such as high schools or museums. their average height from the ground is 14.6 m. because these buildings and centers are located in residential areas and are highly accessible, measurements from these stations represent the air that the citizens breathe. a total of 15 stations are located at road sides, such as main intersections or public transport stations, where the floating population is very high. because data from the roadside stations might show different trends than the data from the residential area stations and the roadside stations were not located in all districts, data from the roadside stations were excluded. air pollutants are hypothesized to affect the mental status through activation of inflammatory processes, the alteration of immune system, influence on oxidative stress, and alterations in cerebral neurotransmitter concentrations. because absorption and chemical reactions take time, using the daily mean concentrations of pollutants rather than other values, such as the maximum, is a reasonable approach. although most studies use daily mean concentrations of air pollutants except for o 3 , one journal uses the standard deviations of air pollutants (pm 10 ) as well as the daily mean concentrations [19] . because air pollutants increase and decrease through chemical reactions, the air pollutant concentrations are expected to increase or decrease faster when the daily mean concentration is higher. because the daily mean concentration and standard deviation were positively associated, as mentioned in one article [19] , we only used the daily mean concentration. in most studies, researchers use daily maximal 8-hour averages [20, 21] or the daily maximum values between 0900 and 1800 h in the case of o 3 [22] . this approach is reasonable, because the main cause of o 3 is ultraviolet waves generated by the sun. however, the pollution ozone can be produced by traffic exhaust which may be increased in the evening to night time in a metropolis. [23] nonetheless, in our data, the o 3 concentrations were sometimes higher during the night than during the day. because using the daily maximal 8-hour average of o 3 would represent a time bias, we used the daily mean o 3 concentration. three time-series analyses in china investigated the associations between air pollution and hospital admissions for psychiatric diseases. the study in tianjin reported that an increase of 10 μg/m 3 in the 2-day average concentrations of pm 10 , so 2 , and no 2 corresponded to increases in daily hospital admissions of 0.15%, 0.49%, and 0.57%, respectively [24] . according to a study in shanghai, increases in pm 10 , so 2 , and co increased hospital admissions for psychiatric diseases by 1.27%, 6.88%, and 0.16% per 10 μg/m 3 increase, respectively [25] . the study in beijing reported that pm 10 showed a significant association with hospital admissions for psychiatric diseases [26] . although the results of the three studies were different, pm 10 was commonly associated with hospital admissions for psychiatric diseases. the types of pollutants that showed significant associations with emergency room visits varied by study, as did the extent to which air pollutants affected hospital visits. these inconsistent outcomes may be due to the different climatic environments of different cities. unlike korea, the reason for the significant results in china may be that the pm 2.5 concentration in china is 203 times higher than the concentration. although pm 2.5 had a significant effect over a time span longer than 3 days, we only evaluated the association between pm 2.5 and ed visits for a lag of 1 to 3 days. previous studies have included longer lags for mortality outcomes due to pollutants. however, a maximum lag of three days was used in the gam model in this study to test the abrupt association between exposure and outcomes. some studies reported significant associations of specific subtypes of psychiatric diseases with air pollutants. both the study conducted in seoul, korea, and the study conducted in canada reported that so 2 , pm 10 , no 2 , and co were positively associated with emergency department visits for depression [11, 12] . the study in beijing also reported that an increase in the pm 10 concentration of 10 μg/m 3 corresponded to an increase in hospital admissions for schizophrenia of 1.74% [26] . in the study conducted in seoul, korea, the association was more significant when the patients were older and had background illnesses, such as cardiovascular diseases and diabetes mellitus. in the gam models, we adjusted for weather factors, such as the daily mean temperature and humidity. those weather factors were fig. 3 . correlation analysis between ed visits, pollutants, and weather. ed, emergency department pm 2.5 , particular mass b2.5 μm pm 10 , particular mass b10 μm o 3 , trioxide (ozone) no 2 , nitric dioxide co, carbon oxide so 2 , sulfur dioxide. correlated with ed visits for psychiatric diseases (p b 0.001, and p = 0.0038, respectively). although 35 awss in seoul measure weather factors, not all 35 awss measure relative humidity and air pressure. therefore, we used data from one of the central station named 'seoul' located in jongro district. the korean meteorological administration also uses the measurement values from this 'seoul' station as representative weather values for seoul. we measured the numbers of ed visits for psychiatric disease. the nedis database was started to collect basic, clinical, diagnostic, and prognostic information for all emergency department patients in 2004. the data are used for ed evaluation programs by the ministry of health and welfare and for reimbursement of the national health insurance program. although the diagnostic codes in usual claims data may be incorrect in number of patients, nedis is required to include the exact diagnostic codes for the annual national evaluation program for all eds. the study was performed in seoul, which is located in east asia with four distinguishable seasons. these study findings may not be generalizable to other cities and climates. based on a two-year observational study in a metropolis, an increase in pm 2.5 shows significant associations with emergency department visits for all psychiatric diseases (f00-f99) and neurotic, stress-related and somatoform disorders (f40-f49) after a lag of one day. however, pm 2.5 did not increase the risk of or exacerbate other psychiatric diseases, such as major depression (mood disorder) or psychosis (schizophrenia). additional research could develop a public health alert system for specific air pollutants associated with psychiatric emergencies, which could be used to prevent psychiatric emergencies in vulnerable populations. this study was supported and funded by the korea centers for disease control & prevention (no. 2017p140200). the study was approved by the institutional review board of the study institution and informed consent was waivered. the all databases were opened to public to be used in researches and did not have any individual private information. this manuscript is an original article, all of the authors have agreed to the submission and the manuscript is not under consideration by any other journal. adjusted relative risks (arrs) with 95 confidence intervals (95% cis) were calculated using general additive models: log [e(y)] = β0 + β(pollutants) + s1(pollutants) + s1(temperature) + s2(humidity) + sp(number) + β(pollutants) + parameters (week, season, middle east respiratory syndrome period) (degree of freedom = 3). the beta coefficients of pm 2.5 were calculated with relative risks with 95% confidence intervals; pm 2.5 , particular mass b2.5 μm (μg/m 3 ); pm 10 health in 2015: from mdgs, millennium development goals to sdgs, sustainable development goals. world health organization epidemiology of adult psychiatric visits to us emergency departments a comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the global burden of disease study association between air pollution and cardiovascular mortality in china: a systematic review and meta-analysis associations of short-term exposure to air pollution with respiratory hospital admissions in arak hourly differences in air pollution and risk of respiratory disease in the elderly: a time-stratified case-crossover study short-term changes in ambient particulate matter and risk of stroke: a systematic review and meta-analysis short-term air pollution exposure aggravates parkinson's disease in a population-based cohort air pollution and emergency department visits for depression in edmonton, canada air pollution and emergency department visits for depression: a multicity case-crossover study air pollution and daily emergency department visits for depression air pollution as a risk factor for depressive episode in patients with cardiovascular disease, diabetes mellitus, or asthma cytokines sing the blues: inflammation and the pathogenesis of depression activation of the stress axis and neurochemical alterations in specific brain areas by concentrated ambient particle exposure with concomitant allergic airway disease comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain the effects of celebrity suicide on copycat suicide attempt: a multi-center observational study the effect of atmosphere temperature on out-of-hospital cardiac arrest outcomes ambient air pollution and out-ofhospital cardiac arrest evaluating the effect of daily pm 10 variation on mortality ambient air pollution and outof-hospital cardiac arrest ambient air pollution and daily hospital admissions for mental disorders in air pollution and symptoms of depression in elderly adults impact of london's road traffic air and noise pollution on birth weight: retrospective population based cohort study season, sex and age as modifiers in the association of psychosis morbidity with air pollutants: a rising problem in a chinese metropolis ambient air pollution and daily hospital admissions for mental disorders in shanghai particulate matter air pollution associated with hospital admissions for mental disorders: a time-series study in beijing, china this study was supported by the korea centers for disease control and prevention (cdc). the study was funded by the korea cdc (no. 2017p140200). key: cord-344120-7t5ce2hb authors: baroutjian, amanda; sanchez, carol; boneva, dessy; mckenney, mark; elkbuli, adel title: sars-cov-2 pharmacologic therapies and their safety/effectiveness according to level of evidence date: 2020-09-01 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.091 sha: doc_id: 344120 cord_uid: 7t5ce2hb introduction: there is a pressing need for covid-19 transmission control and effective treatments. we aim to evaluate the safety and effectiveness of sars-cov-2 pharmacologic therapies as of august 2, 2020 according to study level of evidence. methods: pubmed, sciencedirect, cochrane library, jama network and pnas were searched. the following keywords were used: ((covid-19) or (sars-cov-2)) and ((((((therapeutics) or (treatment)) or (vaccine)) or (hydroxychloroquine)) or (antiviral)) or (prognosis)). results included peer-reviewed studies published in english. results: 15 peer-reviewed articles met study inclusion criteria, of which 14 were rcts and one was a systematic review with meta-analysis. the following pharmacologic therapies were evaluated: chloroquine (cq), hydroxychloroquine (hcq), antivirals therapies, plasma therapy, anti-inflammatories, and a vaccine. conclusion: according to level 1 evidence reviewed here, the most effective sars-co-v-2 pharmacologic treatments include remdesivir for mild to severe disease, and a triple regimen therapy consisting of lopinavir-ritonavir, ribavirin and interferon beta-1b for mild to moderate disease. also, dexamethasone significantly reduced mortality in those requiring respiratory support. however, there is still a great need for detailed level 1 evidence on pharmacologic therapies. introduction also showed that the high-dose group had a higher incidence of qt prolongation greater than 500ms. following an unplanned interim analysis of study findings due to cq dosages related safety concerns, the study independent data safety and monitoring board (dsmb) recommended the immediate interruption of the trial for patients on high dose cq from all age groups, unmasking, and converting all to low dose cq. 13 they concluded that patients with severe covid-19 should not be given a high dose of cq especially with azithromycin and oseltamivir due to risk of qt prolongation and associated lethality. however, findings from patients with prolonged qt showed no clear association between the first day of prolonged qt and day of death, and that cumulative dosages were not higher among prolonged qt associated fatalities. 13 in addition, it is important to be aware that this study had a small sample size, lacked of a placebo control group and used a historical control group. instead, findings were only adjusted by age, and pre-protocol analysis was not conducted due to inability to register daily untaken or mistaken cq doses because or renal or liver failures. 13 an open label rct conducted on patients 18 years and older with mild or moderate ongoing sars cov-2 investigated the effects of hydroxychloroquine (hcq) on negative conversion by 28 days. 14 patients were administered 1200 mg of hcq daily for three days followed by a maintenance dose of 800 mg daily (11 days if mild, 18 days if moderate). 14 results showed that those treated with standard care plus hcq had an 85.4% probability of negative conversion by day 28 (95% ci 73. 8-93.8) , whereas those treated with standard care alone had an 81.3% chance (95% ci 71. 2-89.6 ). 14 however, this difference was reportedly not significant. due to the trial ending early and only two patients (out of 150) with severe disease being enrolled, results on clinical improvement were not presented. 14 this study was limited by its underpowered sample size, non-computerized randomization protocol, and open label design. 14 a more recent, multicenter, open-labeled controlled trial was conducted to assess the efficacy of hcq with and without azithromycin compared to the standard of care. 15 the study was performed on patients with suspected or confirmed mild to moderate covid-19 with 14 or fewer days since symptom onset. patients in the hcq group received a dose of 400 mg twice daily for seven days. patients in the hcq plus j o u r n a l p r e -p r o o f azithromycin additionally received a dose of 500 mg of azithromycin once daily for seven days. clinical status at 15 days was evaluated using a 7-level ordinal scale. results showed no significant difference in the 7-level ordinal scale at 15 days between those treated with hcq and standard care (or 1.21, 95% ci 0.69-2.11, p=1.00), or between those treated with hcq + azithromycin and standard care (or 0.99, 95% ci 0.57-1.73, p=1.00). 15 there were also no significant differences in the number of days free from respiratory support, use of high-flow nasal cannula or non-invasive ventilation, use of mechanical ventilation, duration of hospital stay, in-hospital death, thromboembolic complications, or acute kidney injury between the groups. 15 they also found that prolongation of qt interval was more frequent in the experimental groups (especially the hcq plus azithromycin group), and elevation of liver enzymes was more frequent in the hcq plus azithromycin group than the control group. 15 limitations of this study include lack of blinding, concomitant treatment of patients with other pharmacologic agents, and the fact that some patients were previously treated with hcq ± azithromycin at other hospitals prior to enrollment in this trial. 15 another rct was conducted to assess the efficacy of hcq as a post-exposure prophylaxis. 16 participants were adults with household or occupational exposure to someone with laboratory confirmed covid-19 at a distance of less than 6 ft for more than 10 minutes without a face mask and/or eye shield. time from exposure to enrollment varied between 1-4 days in all participants. patients in the hcq group were administered 800 mg hcq once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days for a total course of 5 days. results showed that the incidence of new illness compatible with covid-19 did not significantly differ between participants receiving hcq (11.8%) and placebo (14.3%) (p=0.35). 16 also, there was no meaningful difference in the effectiveness according to the time of starting post-exposure prophylaxis. 16 side effects were significantly more frequent in the hcq group by day 5 (p<0.001), with nausea, loose stools and abdominal discomfort being the most commonly reported side effects. 16 no serious adverse reactions or cardiac arrhythmias were reported. this study is limited by its use of an a priori symptomatic case definition in some patients as opposed to diagnostic testing. 16 j o u r n a l p r e -p r o o f ii. preliminary results of a double-blind randomized controlled trial by beigel et al. suggest that a 10-day course of remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) is superior to placebo. this study, which was conducted in 60 sites throughout the world, analyzed 1,059 patients and aimed to assess the effect of remdesivir on time to recovery, clinical improvement, and mortality in patients with varying baseline severity. 17 those who received remdesivir had a statistically significant different median recovery time than placebo, 11 days vs 15 days (rate ratio for recovery, 1.32; 95% ci, 1.12 to 1.55; p<0.001). 17 the authors additionally stratified these results by disease severity, where the beneficial effects of remdesivir appeared to be more pronounced in the severe disease stratum. also, the remdesivir group had higher odds of improvement in the 8-level ordinal scale score at day 15 compared to placebo (or 1.50, 95% ci 1.18-1.91). 17 although mortality was numerically lower in the remdesivir group, this difference was not statistically significant. 17 patients on remdesivir who were receiving high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation did not achieve significant differences compared to placebo. 17 another double blind, placebo-controlled, multicenter rct was conducted on the effectiveness of remdesivir in confirmed sars-cov-2 positive patients with severe covid-19. 18 patients were either assigned to receive intravenous remdesivir or placebo infusions. remdesivir was administered at 200 mg on day 1 followed by 100 mg on days 2-10. their primary outcome was time to clinical improvement within 28 days after randomization. some patients were concomitantly treated with corticosteroids, lopinavir-ritonavir or interferons. intention to treat analysis revealed a non-significant decrease in the time to clinical improvement for the remdesivir group compared to placebo. survival at 28 days and clinical improvement at 14 and 28 days were also not statistically significantly different, although numerically higher in the remdesivir group. serious adverse events occurred in 18% and 26% of the remdesivir and placebo groups respectively. 18 intravenous remdesivir did not provide significant improvements in j o u r n a l p r e -p r o o f patients with severe covid-19. this study was limited by insufficient power, the late initiation of therapy and absence of data on viral recovery. 18 another rct evaluated the efficacy of remdesivir therapy after a 5-or 10-day regimen in patients with varying baseline clinical status. 19 clinical status on day 14 as measured by a 7-point ordinal scale was the primary endpoint. patients were administered 200 mg of remdesivir on day 1, followed by 100 mg once daily for the next 4 or 9 days. results showed that clinical improvement of 2 points or more occurred in 65% of patients in the 5-day group and 54% of patients in the 10-day group. 19 after correction of imbalance of baseline clinical status, clinical status at day 14 was similar between the 5-day and 10-day groups (p=0.14). it was concluded that there was no significant difference in efficacy between a 5-day or 10-day course. this study is limited by the fact that the patients in the 10-day group had a significantly worse clinical status than those in the 5-day group (p=0.02), however the authors state that results were adjusted for this discrepancy. 19 other limitations include lack of placebo and the open-label design. 19 one clinical trial was conducted on 14-day triple medication protocols compared to 14-day lopinavirritonavir therapy alone. 20 this open-label, randomized trial tested a triple medication regimen including interferon beta-1b, lopinavir-ritonavir, and ribavirin. patients enrolled had mild to moderate covid-19. the dosage for the experimental group was lopinavir 400 mg and ritonavir 100 mg every 12h, ribavirin 400 mg every 12h, and three doses of 8 million iu of interferon beta-1b on alternate days. the control group received 14 days of lopinavir 400 mg and ritonavir 100 mg every 12h. patients who were admitted to the clinical trial after the 7th day of experiencing symptoms were not treated with interferon beta-1b due to its proinflammatory properties. their primary outcome measure was time to a negative rt-pcr assay by nasopharyngeal swab. the combination group had a significantly shorter median time to a negative rt-pcr than the control group. a negative sars-cov-2 was achieved in a median time of 7 days in the experimental group vs 12 in the control. additionally, clinical improvement was significantly better in the experimental group than the control with a median time to alleviation of symptoms of 4 vs 8 days. 20 this study had an open-label design, absence of placebo group, and was also confounded by j o u r n a l p r e -p r o o f subgroup omitting of interferon beta-1b within the combination group, depending on time from symptom onset. 20 another randomized controlled open-label trial in 199 hospitalized patients with confirmed sars-cov-2 with severe covid-19 was done to compare the clinical effectiveness of lopinavir-ritonavir to standard care alone. 21 severe covid-19 was defined as sars-cov-2 positivity, pneumonia confirmed by chest imaging, and an oxygen saturation of 94% or less while breathing ambient air or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen at or below 300 mg hg. patients in the experimental group were treated with 400 mg/100 mg of lopinavir-ritonavir for 14 days. the time to clinical improvement, mortality at day 28, and detectable viral load were not significantly different between groups. 21 limitations of this study include a non-blinded protocol, higher baseline throat viral loads in the lopinavir-ritonavir group, and absence of data on lopinavir exposure levels in severe and critically ill patients. 21 a more recent rct done on patients with mild to moderate covid-19 aimed to compare the difference in rate of positive-to-negative conversion of sars-cov-2 nucleic acid between lopinavir/ritonavir and arbidol (umifenovir). 22 patients were administered either 400mg/100mg lopinavir/ritonavir po twice daily for 7-14 days, or 200 mg of umifenovir po three times daily for 7-14 days. results showed no significant difference in the rate of positive-to-negative conversion between the lopinavir/ritonavir, arbidol, and control groups (p>0.05). 22 there was also no significant differences between the groups for the rates of antipyresis, cough alleviation, or improvement of ct findings at day 7 or 14 (p>0.05). 22 the lopinavir/ritonavir and arbidol groups experienced adverse effects; whereas the control group did not. 22 limitations include small sample size, single center design, and lack of blinding to clinicians who recruited patients and research staff. 22 iii. anti-inflammatory agents j o u r n a l p r e -p r o o f a multicenter, single-blind rct was conducted to assess the time to clinical improvement in patients with severe covid-19 treated with ruxolitinib, a jak inhibitor. 23 time to clinical improvement was measured as time from randomization to an improvement of 2 points on a 7-category ordinal scale, or live discharge from the hospital. patients in the experimental group received 5 mg twice daily of ruxolitinib. results showed that ruxolitinib plus standard-of-care was associated with a non-statistically significant decrease in median time clinical improvement (12 [iqr, [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] days vs. 15 [iqr, 10-18] days). 23 however, 90% of ruxolitinib patients had significant ct improvement at day 14 compared to 61.9% of control patients (p=0.0495), and levels of 7 cytokines (including il-6, il-12 and vegf) were significantly decreased in the experimental group, demonstrating the anti-inflammatory effects of ruxolitinib. 23 also, the 28-day overall mortality was 0% in the experimental group and 14.3% in the control group. 23 this study is limited by its small sample size, use of an ordinal scale to assess primary end points, concomitantly treatment of some patients with other pharmacologic agents, and lack of inclusion of critically ill patients and patients with invasive ventilator dependence. 23 a preliminary, open-label rct was conducted to assess the effect of dexamethasone on 28-day mortality in hospitalized patients with clinically suspected or laboratory confirmed sars-cov-2 infection. 24 a randomized, double-blind, placebo-controlled trial was conducted to assess the effectiveness of an ad5-vectored covid-19 vaccine. 25 there were two experimental groups, one of which received a higher dose of viral particles (1 x 10 11 particles) and another that received a lower dose of viral particles (5 x 10 10 particles). participants who received either a low or high dose of viral particles had a significant increase in rbd-specific elisa antibodies, seroconversion rates, and neutralizing antibody responses compared to the placebo group. 25 the placebo group showed no increase in antibody from baseline, and no ifnγ-elispot responses. 25 severe adverse reactions occurred in 9% of the high dose patients and 1% of the low dose patients, although no serious adverse reactions were documented. 25 it is important to note that 52% of participants had high pre-existing immunity, and 48% of the participants had low pre-existing immunity. 25 the authors also did not calculate sample size based on study power in advance, and only reported data within 28 days of vaccination. 25 another rct sought to evaluate the effects of convalescent plasma therapy on the time to clinical improvement within 28 days in patients with severe or life threatening covid-19. 26 according to the level 1 evidence reviewed here, the most effective treatments against sars-cov-2, measured by time to negative rt-pcr and time to clinical improvement, are remdesivir therapy and a triple medication regimen (lopinavir-ritonavir, ribavirin, and interferon beta-1b). [17] [18] 20 remdesivir showed beneficial effects in patients with varying baseline severity. it resulted in a decrease in mean recovery time, higher odds of improvement on an 8-level ordinal scale at day 15, and a non-statistically significant decrease in mortality in patients with mild to severe covid-19. 17 it also resulted in a nonstatistically significant reduction in time to clinical improvement in patients with severe covid-19 with no effect on mortality. 18 one reason for not finding a significant effect of remdesivir in severe covid-19 patients could be insufficient power. 18 remdesivir also appears to have some beneficial effects in severe j o u r n a l p r e -p r o o f covid-19 patients irrespective of the time to initiation of therapy. 18 however, there was no difference in clinical improvement between a 5-day and 10-day course of remdesivir in patients with varying baseline clinical status. 19 in patients with mild to moderate covid-19, the triple medication regimen appeared to be most beneficial, as it resulted in a significantly shorter median time to negative rt-pcr compared to therapy with just lopinavir-ritonavir. 20 evidence gathered from other rcts show several additional findings. first, in patients with severe covid-19, treatment with lopinavir-ritonavir showed no significant difference in time to clinical improvement, mortality at day 28, or detectable viral load compared to standard care alone. 21 also, treatment with lopinavir/ritonavir did not significantly affect the rate of positive-to-negative conversion when compared to arbidol in patients with mild to moderate covid-19. 22 second, mortality and qt prolongation was worse in severely ill patients taking high doses of cq compared to low doses. 13 qt prolongation was also significantly higher in patients with mild to moderate covid-19 treated with hcq and hcq plus azithromycin. 15 additionally, hcq showed no significant effect on the probability of negative conversion by day 28 or virologic cure compared to standard care alone in patients with mild to moderate covid-19. 14,27 it also did not reduce the prevalence of unfavorable secondary outcomes such as need for respiratory support, mechanical ventilation, or thromboembolic complications in patients with mild to moderate covid-19. 15 moreover, hcq did not reduce the incidence of new illness when used as a post-exposure prophylaxis. 16 however, meta-analysis did reveal that hcq treatment resulted in fewer cases of radiological progression of lung damage. 27 furthermore, treatment of severe covid-19 patients with ruxolitinib resulted in a non-statistically significant decrease in median time to clinical improvement, and a statistically significant decrease in levels of seven cytokines including il-6, il-12 and vegf, indicating that it may be useful in treating cytokine storm. 23 convalescent plasma was also efficacious in reducing the time to clinical improvement in severe and life threatening covid-19. 26 oral or intravenous dexamethasone was shown to significantly reduce mortality among hospitalized covid-19 patients j o u r n a l p r e -p r o o f receiving mechanical ventilation or oxygen without mechanical ventilation. 24 finally, vaccination of healthy individuals using an ad5-vectored covid-19 vaccine showed significant increase in immunity to sars-cov-2 by 28 days. 25 while we await higher quality evidence from randomized control trials and meta-analyses, these results provide some context on the efficacy of pharmacologic therapy in covid-19 patients. as of may 20, 2020, the fda has granted emergency use authorization for intravenous remdesivir for severe covid-19. 28 however, they have revoked emergency use authorization for use of hydroxychloroquine and chloroquine due to their high risk to benefit ratio. 28 covid-19 has undoubtedly posed a detrimental health burden worldwide. there is still a great need for detailed evidence on individual pharmacologic therapies. the findings from our review suggest that there is currently inconclusive evidence for one therapy. it is difficult to conduct studies on one category of pharmacologic treatment due to the lack of a universal systematic approach to treating covid-19. in the absence of a vaccine available to the public, there is a great need for level 1 evidence from randomized controlled trials and meta-analyses to support the development of evidence-based guidelines to treat covid-19 patients. aside from being novel, part of what makes treatment of sars-cov-2 difficult is its ability to affect multiple organ systems. 29 the disease is characterized as an acute respiratory failure but may have systemic outcomes such as gastrointestinal, cardiovascular, and nervous system symptoms in addition to multi-organ failure. there has been evidence of high incidence of pulmonary embolism and thrombotic events. these severe cases often present with thrombocytopenia, elevated d-dimer levels, and pt prolongation. the hypercoagulable state often seen in covid-19 patients can be explained by the j o u r n a l p r e -p r o o f overwhelming production of inflammatory cytokines. this increase in inflammatory markers leads to an activation of the coagulation cascade and inhibits the fibrinolytic pathway. 29 36 being over 50 years old had a significantly larger impact on mortality than sex at birth and preexisting comorbidities. 36 another important point to be discussed is the increase of non-evidence-based treatment and the unintended morbidity and mortality that results from it. there has been a large increase in the spread of false information and non-evidence-based remedies, such as consumption of cow urine and high proof alcohol that have resulted in illness and even death. 37 furthermore, there has been a recent concern for patients who are using ace-inhibitors. a casepopulation study in spain on the admission rate of covid-19 patients on ace-inhibitors compared to other antihypertensive medications revealed that there was no increased risk of covid-19 related admission to a hospital, and concluded that ace-inhibitors not be discontinued. 38 however, there remains a concern, especially among uninformed providers and patients, on whether use of ace-inhibitors pose a risk to patients during this pandemic. a similar review done by sanders et al. on pharmacologic treatment for covid-19 report similar findings regarding the available pharmacologic options and the inconclusive nature of the available data on these drugs. 39 they additionally offer useful resources for clinical treatment guidance. in contrast, we have tailored our review to provide a more up to date, in-depth and systematic analysis using only level 1 evidence. additionally, our discussion touches on the multisystem effects of sars-cov-2. undoubtedly, it is of utmost importance to discuss the safety profile of all the medications included. many of these pharmacologic agents result in side effects ranging from mild to severe. first, hcq and cq have both been shown to cause cardiac electrical disturbances and cardiomyopathy. 40 one clinical trial using a dose of 600 mg twice daily for ten days was terminated early due to the death of 11 patients as a result of arrhythmias by the 6th day. 13 other adverse effects associated with hcq include retinopathy, gastrointestinal disturbances, and suicidal behavior. 41 additionally, agents like hcq and cq can cause qt prolongation and their toxicity may be exacerbated when combined with other agents that also prolong the qt interval, such as azithromycin. 42 patients who develop qt prolongation without torsades de pointes should be treated immediately by correcting oxygen, potassium, calcium, and magnesium concentrations. magnesium sulphate is recommended as the first-line therapy for torsades de pointes. 43 cardiotoxicity has not been reported with remdesivir use. however, side effects of remdesivir include allergic reactions and increased liver enzymes. 44 adverse effects associated with triple therapy j o u r n a l p r e -p r o o f using interferon beta 1b, lopinavir-ritonavir and ribavirin include diarrhea, nausea, and increased alanine transaminase levels, all of which stopped in one trial upon discontinuation of the drugs. 20 additional side effect concerns with lopinavir-ritonavir include haptic injury, pancreatitis, acute gastritis, and qt prolongation. 21 use of ruxolitinib in covid-19 patients showed a favorable side-effect profile of the drug according to the rct reviewed in this study. 23 some of the adverse reactions included mild anemias, neutrocytopenia, thrombocytopenia, elevated liver enzyme levels, dizziness, rash, and nausea. 23 there were no serious adverse events such as acute heart failure, shock, and sepsis. 23 adverse reactions of dexamethasone were not evaluated in the rct included in this study; however, clinicians treating covid-19 patients with dexamethasone should monitor their patients for hyperglycemia, secondary infections, psychiatric effects and avascular necrosis. 45 the ad5-vectored vaccine also showed a favorable side-effect profile with most side effects being a result of the injection itself such as skin induration, redness, and swelling. 25 the systemic side effects reported were headache, vomiting, diarrhea, joint pain, muscle pain, fatigue, headache, and cough. 25 lastly, adverse effects associated with the convalescent plasma trial included dyspnea, fever, and an allergic reaction caused by transfusion. 26 these findings lead us to recommend that physicians follow updated guidelines from reputable sources. the society of surgical oncology also offers frequently updated resources to assist physicians in treating particularly vulnerable patients with cancer. 46 currently, there is also a great deal of randomized clinical trials that are ongoing and should provide the medical community with more conclusive evidence in the near future. according to the nih, there are 2,962 active studies on covid-19 as of august 2, 2020. 47 the studies included in this review had several limitations. first, there was an issue of small sample size for several studies. 13, [22] [23] 26 another limitation to the findings is the inability to generalize them to all patients as a result of specific exclusion criteria such as individuals with mild or severe disease. [13] [14] [15] 18, [20] [21] [22] [23] 26 also, several studies reviewed above aimed to focus on the efficacy and safety of one drug, but employed multiple drugs in the treatment of patients. 15, 18, 23 these limitations make it difficult to compare j o u r n a l p r e -p r o o f journal pre-proof the efficacy and safety profiles of the drugs being used. the findings listed are dependent on the accuracy and validity of data used to assess sars-cov-2 pharmacological therapies. lastly, given the rapidly evolving nature of this pandemic, it is difficult to ensure that all the existing evidence has been included up until this article's publication date and new information and trials will arriving. there remains uncertainty regarding the safest and most effective pharmacologic therapy for covid-19 disease. however, the findings from this review conclude that, according to level 1 evidence, remdesivir therapy in mild to severe disease, and the triple medication regimen (lopinavir-ritonavir, ribavirin and interferon beta-1b) in mild to moderate disease are the most efficacious against sars-cov-2 in terms of symptom improvement and time to a negative rt-pcr. also, dexamethasone was significantly able to reduce mortality in patients receiving respiratory support. we recommend that physicians remain informed on up to date evidence such as preliminary data from rcts, and work with their institution and scientific societies in developing evidence-based systematic guidelines in the treatment of covid-19 patients. j o u r n a l p r e -p r o o f hospitalized patients with clinical suspicion of covid-19, aged 18 years or older, with respiratory rate higher than 24 rpm and/or heart rate higher than 125 bpm (in the absence of fever) and/or peripheral oxygen saturation lower than 90% in ambient air and/or shock. participants who received either a low or high viral particles dose had a significant increase in rbd-specific elisa antibodies, seroconversion rates and neutralizing antibody responses compared to the placebo group. placebo group showed no antibody increase from baseline. no ifnγ-elispot responses in placebo group. points on a 6-point disease severity scale, or discharge. clinical improvement occurred at a higher rate in those with severe disease compared to those with life threatening disease (91.3% vs 68.2%). there was no significant difference in 28day mortality (or 0.65, 95% ci 0.29-1.46) or time to discharge (hr 1.61, 95% ci 0.88-2.93). use of convalescent plasma resulted in an 87.2% negative conversion rate of viral pcr at 72 hours compared to 37.5% in the control group. zoonotic origins of human coronaviruses epidemiology, pathogenesis, and control of covid-19 covid-19 situation report-195 clinical, laboratory and imaging features of covid-19: a systematic review and meta-analysis epidemiology, pathogenesis, and control of covid-19 current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (covid-19) advice on the use of point-of-care immunodiagnostic tests for covid-19 profiling early humoral response to diagnose novel coronavirus disease (covid-19) us food and drug administration clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china clinical features of patients infected with 2019 novel coronavirus in wuhan, china the levels of evidence and their role in evidence-based medicine effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection: a randomized clinical trial hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial hydroxychloroquine with or without azithromycin in mild-to-moderate covid-19 a randomized trial of hydroxychloroquine as postexposure prophylaxis for covid-19 remdesivir for the treatment of covid-19 -preliminary report remdesivir in adults with severe covid-19: a randomised, double-blind, placebo-controlled, multicentre trial remdesivir for 5 or 10 days in patients with severe covid-19 triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with covid-19: an open-label, randomised, phase 2 trial a trial of lopinavir-ritonavir in adults hospitalized with severe covid-19 efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate covid-19: an exploratory randomized controlled trial ruxolitinib in treatment of severe coronavirus disease 2019 (covid-19): a multicenter, single-blind, randomized controlled trial dexamethasone in hospitalized patients with covid-19 -preliminary report immunogenicity and safety of a recombinant adenovirus type-5-vectored covid-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebocontrolled, phase 2 trial effect of convalescent plasma therapy on time to clinical improvement in 28 covid-19 -toward a comprehensive understanding of the disease identification of a potential mechanism of acute kidney injury during the covid-19 outbreak: a study based on single-cell transcriptome analysis imaging & other potential predictors of deterioration in covid-19 assessment of qt intervals in a case series of patients with coronavirus disease 2019 (covid-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit gastrointestinal complications in critically ill patients with covid-19 patients with cancer appear more vulnerable to sars-cov-2: a multicenter study during the covid-19 outbreak features of 20 133 uk patients in hospital with covid-19 using the isaric who clinical characterisation protocol: prospective observational cohort study non-evidenced based treatment: an unintended cause of morbidity and mortality related to covid-19 use of renin-angiotensin-aldosterone system inhibitors and risk of covid-19 requiring admission to hospital: a case-population study pharmacologic treatments for coronavirus disease 2019 (covid-19): a review cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature risk of using hydroxychloroquine as a treatment of covid-19 safety considerations for chloroquine and hydroxychloroquine in the treatment of covid-19 pharmacological treatment of acquired qt prolongation and torsades de pointes us food and drug administration key: cord-258662-6y45gb0t authors: butt, nausharwan; arshid, awais; ahmad, sarah aftab; khalid, nauman; kayani, waleed tallat title: cardiovascular complications in covid-19 date: 2020-07-19 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.032 sha: doc_id: 258662 cord_uid: 6y45gb0t nan in summary, covid-19 is associated with significant cardiovascular complications which may also include pericarditis, pericardial effusion and takotsubo (stress) cardiomyopathy. further larger studies are required to evaluate this association. cardiovascular complications in covid-19 sars-cov-2 detection in the pericardial fluid of a patient with cardiac tamponade covid-19 (sars-cov-2) and the heart -an ominous association all authors have no sources of funding to disclose the authors have no conflict of interest to declare. key: cord-294736-ji4jz3h6 authors: beşler, muhammed said; arslan, halil title: acute myocarditis associated with covid-19 infection() date: 2020-06-02 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.100 sha: doc_id: 294736 cord_uid: ji4jz3h6 we present the case of a 20-year-old male patient without previous history of cardiovascular disease who was admitted to our hospital with a new onset febrile sensation and chest pain. chest computed tomography revealed a subpleural consolidation with a halo of ground-glass opacification. blood tests revealed elevated levels of markers of myocyte necrosis (troponin i and creatine kinase–mb). nasopharyngeal swab was positive for covid-19. cardiac mri showed myocardial edema and late gadolinium enhancement compatible with myocarditis associated with covid-19 infection. this case showed that acute myocarditis can be the initial presentation of patients with covid-19 infection. coronavirus disease 2019 (covid-19) has been declared a world-wide public health emergency. there is limited published data concerning cardiovascular presentations in the wake of viral epidemics [1] . acute or fulminant myocarditis as well as heart failure have been reported with middle east respiratory syndrome coronavirus and could be expected to occur with sars-cov-2, given the similar pathogenicity [2] . previous severe acute respiratory syndrome (sars) beta-coronavirus infections could be associated with tachyarrhythmias and signs and symptoms of heart failure [3] . the current report describes a case of myocarditis in coronaviruses and the cardiovascular system: acute and long-term implications association of coronavirus disease 2019 (covid-19) with myocardial injury and mortality cardiovascular complications of severe acute respiratory syndrome cardiovascular magnetic resonance in myocarditis: a jacc white paper clinical features of patients infected with 2019 novel coronavirus in wuhan cardiac involvement in a patient with coronavirus disease cardiac magnetic resonance assessment of myocarditis european cardiovascular magnetic resonance (eurocmr) registry-multi national results from 57 centers in 15 countries key: cord-308807-9yggo5yk authors: zheng, davidx.; jella, tarun k.; mitri, elie j.; camargo, carlos a. title: national analysis of covid-19 and older emergency physicians date: 2020-11-04 journal: am j emerg med doi: 10.1016/j.ajem.2020.10.074 sha: doc_id: 308807 cord_uid: 9yggo5yk nan . while public health efforts (e.g., statewide stay-at-home orders) had initially flattened the curve, 1 covid-19 spread in the u.s. has once again begun to accelerate. on october 23, 2020, the u.s. reached a new pandemic record of 83,010 daily cases, 1 and all signs point toward an impending "second wave" or "third surge." given the association between advanced age and covid-19 severity, 2 our objective was to compare the geographic distribution of u.s. eps age  60 years to the cumulative distribution of confirmed covid-19 cases, to highlight the potential risks faced by this vulnerable population of clinicians. 4 we integrated both datasets into qgis geospatial analysis software (version 3.12.1), superimposing them onto state boundary files published by the u.s. census bureau. 5 states were grouped into color-coordinated quintiles based on proportion of eps age  60, and a logarithmic scale was used to adjust coordinate data points of cumulative covid-19 cases, resulting in a heatmap depicting the proportion of eps age  60 and covid-19 disease burden for each state. this study was deemed irb exempt due to the use of deidentified and publicly available data. the aamc identified a total of 43,311 clinically active eps in 2018, of whom 10,804 (24.9%) were age  60 years. 3 the 10 states in the highest quintile of older eps were west virginia, new mexico, vermont, hawaii, maine, oklahoma, montana, alabama, arkansas, and arizona ( table 1) consideration, especially as cases continue to surge. emergency departments could also amend operations to prioritize reduction of nosocomial transmission risk among advanced age eps (e.g., allocating critically limited ppe to higher-risk physicians, geographically cohorting patients with suspected or confirmed covid-19 infection within an emergency department). 7 furthermore, prioritization of routine covid-19 testing of older eps, as well as creation of reserve pools of emergency medicine physicians (e.g., eps from hospital systems relatively less affected by covid-19), may facilitate the transfer of care duties from older eps at more heavily affected emergency departments, in the event that they test positive and need to safely self-isolate. 8 study limitations include not controlling for other individual factors associated with increased covid-19 severity (e.g., obesity, black race, hispanic ethnicity), 9,10 as well as using state-level data, which precludes insights into risk differences by, for example, rural/urban status. moreover, we acknowledge that utilizing cumulative case volumes does not account for differences in the present rate of covid-19 spread between states (e.g., rate of covid-19 spread and confirmed case count in new york have since stabilized from march/april 2020). 1 finally, we understand that covid-19 infection among younger clinicians is a serious problem. our hope is that the current findings will raise awareness among eps and assist implementation of safety guidelines and workforce planning. collectively, we need to ensure that all front-line eps, including those at higher risk, are properly protected during the covid-19 pandemic. states were grouped into color-coordinated quintiles based on relative proportion of older eps, and cumulative covid-19 case volumes were adjusted with a logarithmic scale to create proportionally-sized data points. risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in wuhan, china state physician workforce data report esri. covid-19 resources the american college of emergency physicians guide to coronavirus disease (covid-19 redesigning emergency department operations amidst a viral pandemic protecting our healthcare workers during the key: cord-255267-o8k5ep9y authors: gan, connie cai ru; tseng, yu-chi; lee, feng-you; lee, kuan-i title: personal ventilation hood for protecting healthcare workers from aerosol-transmissible diseases date: 2020-07-22 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.036 sha: doc_id: 255267 cord_uid: o8k5ep9y nan the provisional pilot study shows, the hood offers several potential implications. in terms of healthcare workers' safety, the hood ensures lower close contact with the patients, primarily perform medical and surgical procedures that can potentially generate aerosolized particles include intubation and bronchoscopy. it has been observed that efficient containment can be achieved using simple construction and essential medical equipment by considering pressure differential and airflow patterns. this experiment has several limitations. due to clinical restrictions during an outbreak, the simulations only presumed the patient lying on bed without any movement around the room. thus, we are unable to control under any humanenvironment condition, and the air ventilation in the room would have thinned the presence of fluorescent markers on the surfaces. moreover, the environmental sites sampled represent only a small fraction of the total area. further studies are required to validate these initial results. the hood protects patients that would be required to undergo several tests differently, radiology, physical therapy, pulmonary, and laboratory. even in situations where a patient needs to be moved to another facility, the hood could limit the exposure to other patients and hospital personnel. we urged that with the protection provided to both patient and hospital personnel, visitors of the health facility are protected from possible exposure. this result is consistent with other researchers 4-5 that emphasize the need to adapt to the healthcare setting in the wake of the covid-19 pandemic. clinical management of covid-19 are powered air purifying respirators a solution for protecting healthcare workers from emerging aerosol-transmissible diseases? annals of work exposures and health surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) from a symptomatic patient persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents shifting the paradigm -applying universal standards of care to ebola virus disease key: cord-278413-vad80mg5 authors: goldenberg, matthew n.; parwani, vivek title: psychiatric emergency department volume during covid-19 pandemic date: 2020-06-01 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.088 sha: doc_id: 278413 cord_uid: vad80mg5 nan one commonly reported phenomenon in the first months of the covid-19 era in the united states has been the reduction in emergency department (ed) visits and hospitalizations of patients with heart attacks, strokes and other acute, non-covid illnesses. [1] less is known about whether and how the number of patients presenting to eds for psychiatric problems has changed. prior to the pandemic, there were reasons to believe that psychiatric ed visits might increase. many people could experience distress such as anxiety, sadness, grief and anger during this uncertain time. [2] because of physical distancing measures, normal sources of support are less directly accessible. people with pre-existing mental illness may be particularly vulnerable to such change. alterations to outpatient practices may mean that prior mental health treatment could be disrupted. access to social services such as shelters or soup kitchens might decrease. connecticut reported its first case of covid-19 on march 8, 2020. several local school districts shuttered the following week, and the governor issued an order for the suspension of nonessential business and for residents to stay at home effective march 23. as of the end of april, 27,700 cases and 2,257 covid-associated deaths had been reported in the state. [3] yale-new haven hospital (ynhh) is a 1541-bed tertiary care medical center with three local eds (two in downtown new haven and one in a nearby suburb), the sixth largest hospital by bed capacity in the country. the psychiatric emergency service (pes) is staffed 24 hours per day and treats patients 16 years and older. each year, the ed has about 200,000 patient visits per year including roughly 9,000 pes visits. at ynhh, pes and overall ed volumes for january, february and early march 2020 were similar to prior years (see table 1 ). however, starting in the last two weeks of march through the first week in may, pes volume declined about 26%, from an average of 24.2 patients per day to 18 patients per day (see figure 1 ). for the month of april (the first full month of the local outbreak), pes volume was only about 70% of prior years' average. overall ed monthly volume was 58% of prior years' average. roughly the same percentage of psychiatric patients were admitted as in prior years (32% vs. 30.6%); overall ed admission rate was higher than in prior years (35% vs 27%). the reasons for the decline in psychiatric ed visits are likely multiple. patients may have feared contracting the novel coronavirus if they came to the ed. [4] some may have wrongly believed that the hospital was only treating covid-19 or that their problem was not severe enough to warrant emergent treatment . while there may have been more psychic distress in the population overall (reports have suggested increased call volume to helplines [5] , e.g.), ed psychiatry visits may be a poor proxy for overall mental well-being of a community. the rapid establishment of robust outpatient services via telepsychiatry may have preserved or even expanded access to treatment for many patients. increased attention to other social services including housing and food security may have at least temporarily addressed the immediate needs of many vulnerable individuals in the community. pes volume decreased less than overall ed volume, suggesting that patients may be less willing or able to defer their need for acute psychiatric care as opposed to other acute medical care. psychiatric patients may be less able than other patients to identify or utilize alternatives to the ed. some patients do not make the decision to come to the ed themselves, being brought by family, friends or the police. whether some of the relatively preserved volume is due to patients' experiencing pandemic-related distress is not known. the fact that ed patients overall were admitted at a higher rate suggests they were, on average, sicker than usual, perhaps because of delayed help-seeking. that the rate of hospitalization of psychiatric patients was just slightly higher than prior years may indicate that the overall acuity in pes was similar to previous years. to our knowledge, this letter is one of the first formal descriptions of psychiatric ed volume during the unprecedented covid-19 public health crisis in the us. the data presented is from one large academic medical center in a heavily impacted state, so the findings may not be generalizable to other settings. the overall volume data lack granularity and raises additional questions about the drivers of the decreased ed volume that was observed. further study will elucidate how the ed psychiatry patient population during covid-19 compared with prior periods in terms of various demographic factors (e.g. age, gender, race, housing status) and diagnostic categories. such analysis should increase understanding of the decisions of people to seek (or not seek) emergency psychiatric care during a pandemic and help explain the substantial decrease in ed psychiatric volume. ( where have all the heart attacks gone? the new york times mental health and the covid-19 pandemic covid-19 update public poll: emergency care concerns amidst covid-19 flood of calls and texts to crisis hotlines reflects americans' rising anxiety. npr key: cord-257535-v8dwkngi authors: sen-crowe, brendon; mckenney, mark; boneva, dessy; elkbuli, adel title: a state overview of covid19 spread, interventions and preparedness date: 2020-04-11 journal: am j emerg med doi: 10.1016/j.ajem.2020.04.020 sha: doc_id: 257535 cord_uid: v8dwkngi nan the current doubling time in the us for the sars-cov-2, virus, is 3 days 5 . however, the doubling time is currently 6 days for king county in washington state 6 . in mid-march washington state took measures to limit the spread of infection, by closing educational facilities, closing non-essential services, and a stay at home order (saho) 7 . these efforts have been associated with the percent increase in cases and fatalities decreasing ( figure 2 ). according to the institute for disease modeling (idm), the spread of infection into seattle and eastside decreased by about 90% and has continuously decreased since march 2 nd9 . in late february, the reproductive number was about 2.7, whereas it was approximately 1.4 on march 18 th 9 . likewise, in california, with strict physical distancing measures in effect in the bay area and sacramento county, the doubling time is now 6 days 6 . on march 19 th california closed nonessential services and educational facilities, and a saho was enacted 10 . the percent increase in cases in california also decreased after this period ( figure 2 ). additionally, a similar effect was observed after idaho issued a saho and closed non-essential services on march 25 th 11 . after march 25 th the fatality rate increased slightly, and then showed a decreasing trend and lower percent increase in new cases ( figure 2 ). the lack of testing does not appear to play a role in the decrease in fatality rate because the percentage of those testing positive continues to increase ( figure 2 ). florida issued a saho on april 3rd, late in comparison to many other states 12, 13 . however, their percent increase in cases over the past two weeks has decreased comparably to states in which a saho was in effect earlier ( figure 2 ). this highlights the importance of other interventions. florida mandated isolation orders of those at most risk, including senior citizens and those with underlying medical conditions 12 . furthermore, travel was limited to that necessary to obtain or provide essential services or to conduct essential activities, and businesses/organizations were encouraged to provide delivery, carry-out or curbside service 12 . new york holds the greatest number of cases and deaths (figure 1) 1 . this forced the state to consider extraordinary measures aimed at increasing hospital capacity and decreasing density of cases. to address the first issue, an executive order was issued, allowing the state to increase j o u r n a l p r e -p r o o f hospital capacity 14 . in addition, there was deployment of a 1,000-bed hospital ship to new york harbor 15 . moreover, an executive order signed on march 19 th mandated all businesses requiring in-office personnel to decrease their in-office workforce by 75% 16 . another executive order on march 20 th , enforced the closure of all non-essential businesses 17 . the percent increase in cases dropped after these interventions (figure 2 ). the relative increase in cases appears to be abating, but the fatality rate is increasing (figure 2 ). these trends may suggest that there is inadequate healthcare capacity and medical supplies 18 . in response, the centers for medicare & medicaid services (cms) granted changes to provide some flexibility for hospitals, physicians and healthcare organizations 19 . cms allowed hospitals to provide services for patients transferred outside of their building 19 . the new rules allow for patient transfers to ambulatory surgery centers, freeing hospital beds for the critically ill 19 there is an association between implementing social distancing and a lowering of the percent increase of cases. some states implemented interventions earlier than others did, which may be responsible for the differing fatality rates. encouraging states to implement more widespread distancing interventions at an earlier time has the potential to act on multiple levels in preventing the spread of covid-19, and could make all the difference in preserving thousands if not hundreds of thousands of lives in the united states. now is not the time to return to normalcy; we can win this fight together. j o u r n a l p r e -p r o o f the total cases and total deaths plotted as a function of time for washington state (wa), california (ca), new york (ny), florida (fl) and idaho (id). as of april 1, 2020, the total number of cases in descending order is ny > ca > fl > wa > id. the total number of deaths in descending order is ny > wa > ca > fl > id. covid-19 map. johns hopkins coronavirus resource center lung cancer facts: 29 statistics and facts: lcfa. lung cancer foundation of america covid-19) us covid-19 cases surge past 82,000, highest total in world reported covid-19 cases over time proclamation by the governor amending proclamation 20-05. office of the governor understanding the impact of covid-19 policy change in the greater seattle area using mobility data social distancing and mobility reductions have reduced covid-19 transmission in king county executive department -state of california executive order number 20-91. office of the governor department of health announces two presumptive positive covid-19 cases in florida. department of health announces two presumptive positive covid-19 cases in florida | florida department of health during coronavirus briefing, governor cuomo issues executive order allowing state to increase hospital capacity. governor andrew m amid ongoing covid-19 pandemic, governor cuomo announces deployment of 1,000-bed hospital ship 'usns comfort' to new york harbor governor cuomo signs executive order mandating businesses that require in-office personnel to decrease in-office workforce by 75 percent ihme: covid-19 projections trump administration makes sweeping regulatory changes to help u.s. healthcare system address covid-19 patient surge. centers for medicare & medicaid services covid-19 hospital capacity estimates 2020. harvard global health institute us department of health and human services; assistant secretary for preparedness and response administrator for the centers for medicare and medicaid services and member of white house coronavirus task force seema verma interviewed on u.s. preparedness for ongoing coronavirus pandemic figure legends key: cord-317784-fl9zbgad authors: senthilkumaran, subramanian; murugan, koushik; sanjay, patne; thirumalaikolundusubramanian, ponniah title: propofol in covid 19 — from basic science to clinical impact date: 2020-07-09 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.011 sha: doc_id: 317784 cord_uid: fl9zbgad nan j o u r n a l p r e -p r o o f increases angiotensin-converting enzyme2 (ace2) expressions in human endothelial cells as mentioned by sohn [2] . however, recently [3] it was demonstrated that propofol infusion increases ace2 mediated conversion of angiotensin ii to angiotensin, which results in a fall in angiotensin ii levels and an elevation of angiotensin 1 to7; and these exhibit protective effects of lungs by way of recovery of endothelial cell function via an up-regulation of ace2-ang -mas axis, subsequent to phosphorylation of endothelial nitric oxide (no) synthase to generate no, and regulation of apoptosis-related protein such as bcl-2, caspase9. moreover, propofol also increases the concentration of cyclic guanosine monophosphate in cultured endothelial cells through a no dependent mechanism [4] . in addition, propofol exerts its antioxidant property [5, 6] as evidenced by the inhibition of lipid peroxidase production in the platelet membrane and a decrease in tissue consumption of glutathione [7] . interestingly, its ability to inhibit inflammatory response was demonstrated by taniguchi et al. [8] in the form of a reduction in the cytokine response (tnf-alpha and il-8) and neutrophil infiltration in the lungs in endotoxemic rats received propofol infusion. propofol also, prevents the development of metabolic acidosis during endotoxemia [8] . apart from the antiinflammatory response, it also has an antithrombotic effect by way of inhibiting the platelet aggregation possibly in combination with the effects of the solvent, intralipid as well as increases leucocyte nitric oxide production, and inhibition of platelet thromboxane synthesis [9] . in view of the multiple protective actions, fda of usa recently permitted the emergency use of the fresenius propoven 2% emulsion to maintain sedation via continuous infusion for covid-19 patients older than 16 years who require mechanical ventilation [10]. to summarize, propofol a short-acting intravenous sedative-hypnotic agent has multiple actions, including significant antioxidant and anti-inflammatory activities, apart from neuroleptic malignant syndrome in patients with covid-19 propofol and sedation in patients with coronavirus disease propofol prevents human umbilical vein endothelial cell injury from ang ii-induced apoptosis by activating the ace2-(1-7)-mas axis and enos phosphorylation propofol stimulates nitric oxide release from cultured porcine aortic endothelial cells the antioxidant potential of propofol (2,6-diisopropylphenol) effects of propofol on endothelial cells subjected to a peroxynitrite donor propofol: a review of its non-anaesthetic effects effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats antiplatelet effect of the anaesthetic drug propofol: influence of red blood cells and leucocytes key: cord-322887-md446f9p authors: carver, catherine; jones, nicholas title: cardiac injury and ards meta-analysis validity – correspondence in response to santoso et al. date: 2020-06-27 journal: am j emerg med doi: 10.1016/j.ajem.2020.06.028 sha: doc_id: 322887 cord_uid: md446f9p nan in the course of writing a rapid review for the university of oxford, we came across an interesting and timely systematic review and meta-analysis in the american journal of emergency medicine by and colleagues (1). this paper was of note to us because it included a meta-analysis on acute respiratory distress syndrome (ards) and cardiac injury, based on two papers -one by shi (2) and another by wu (3). on reading the paper by wu, we have significant concerns about the inclusion of this study in santoso's meta-analysis as we believe it currently underpins an inaccurate conclusion that cardiac injury is not significantly associated with increased risk of ards in covid-19 by santoso. in figure 3 in santoso, they describe wu as 26 cases of ards (11 cases of ards with cardiac injury, and 15 cases of ards with no cardiac injury). when we examined the wu paper, we found a composite outcome of respiratory failure, ards and sepsis was reported, totalling 26 cases across the different troponin levels ( table 2 in wu) . further, when we studied table 1 in wu, 26 patients are described as having respiratory failure/ards/sepsis. this is broken down as 20 with respiratory failure and 6 with ards or sepsis. even if one assumes that all of those cases were ards, that gives a total of 6 ards cases in this paper, contrasting with the 26 used for santoso's meta-analysis. there are conceivable alternative explanations for these figures, for instance perhaps all of the respiratory failures were caused by ards and wu used a counterintuitive way of presenting the data by separating these out from the 6 ards or sepsis cases. however, from what we currently have access to, it seems most likely that santoso's meta-analysis for ards has been based on composite endpoint data. this is concerning, particularly when there is evidence ards was a minority diagnosis. moreover, the conclusion of santoso runs counter to shi's jama cardiology paper, which was the other paper included in santoso's meta-analysis, which did report on purely ards cases and cardiac injury and did find a statistically significant association. cardiac injury is associated with mortality and critically ill pneumonia in covid-19: a meta-analysis association of cardiac injury with mortality in hospitalized patients with covid-19 in wuhan heart injury signs are associated with higher and earlier mortality in coronavirus disease 2019 (covid-19). medrxiv screening and data extraction in santoso were performed by two authors, which is good practice and reduces the probability of a simple error. we are therefore curious to learn whether the authors had contact with wu et al and have insights into the wu data that are not immediately apparent to readers. if so, we would appreciate santoso et al sharing this information publicly as it would inform our research and no doubt that of others.we look forward to having our confusion addressed by the authors and thank them for their work. key: cord-350045-85jug39x authors: pruc, michal; golik, dawid; szarpak, lukasz; adam, ishag; smereka, jacek title: risk of coronavirus infections among medical personnel date: 2020-05-08 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.017 sha: doc_id: 350045 cord_uid: 85jug39x nan j o u r n a l p r e -p r o o f dear editor, infections from the coronavirus group are a very important problem among medical personnel. this affects both the continuity of work of medical services, due to the compulsory quarantine of infected persons and their abandonment of work, and the insufficient number of employees to replace them in their tasks and duties. due to the current situation of the covid-19 pandemic, we can predict how the morbidity of health care workers will develop based on data on other viruses from the coronavirus group. in global research on sars-cov-1, mers-cov and sars-cov-2, it can be seen that a very large percentage of the number of infected people are health professionals struggling with them in various medical facilities. this is most often due to the fact that medical personnel is incorrectly trained in proper protection against the virus and lack of equipment that meets the relevant standards. 1 in the case of sars-cov-1, medical personnel accounted for 21.07% (1706/8096) of all infections, mers-cov 13.37% (183/1368) 2,3 , sars-cov-2 due to the growing number of infections, however, the total number of infections of medical personnel is unknown, in the uk, in a survey conducted on 17 march 2020 among 5194 physicians, 12.8% were unable to perform work due to symptoms and another 15.1% were unable to perform work due to symptoms among family members. in the netherlands a survey was conducted from 6-8 march 2020 on 1097 health care workers, among whom the percentage of infected was 4.1%. 4 currently, the total number of infected healthcare workers on sars-cov-2 is unknown due to the steadily increasing number of infections and the lack of global data on the problem. the current march data on the prevalence of infection among healthcare professionals from the uk and the netherlands show a huge proportion of infected people in healthcare. 5 the scale of the problem as shown by the percentage of people infected with sars-cov-2 should be considered on a case-by-case basis, as the percentage of people affected is significantly higher than for sars-cov-1 and mers-cov. the data on sars-cov-1 and mers-cov can predict how much health care workers may be infected despite the lack of up-to-date data on sars-cov-2. in view of the high risk of infection transmitted from and to medical personnel, it seems reasonable to implement weekly diagnostic tests to rule out infection with the virus, as well as to limit the possibility for medical personnel to work in different locations at the same time, as experience from china and italy shows that this may pose a high risk of spreading outbreaks. in summary, we skip this extremely important aspect of the fight against the current pandemic, which is the incidence of covid-19 in hcws. what cost we will have to pay for this will show the future, but already now health care systems around the world need to be restructured and the security of medical staff improved immediately. the use of personal protective equipment in the covid-19 pandemic era risk factors for middle east respiratory syndrome coronavirus infection among healthcare personnel risks to healthcare workers with emerging diseases: lessons from mers-cov, ebola, sars, and avian flu roll-out of sars-cov-2 testing for healthcare workers at a large nhs foundation trust in the united kingdom rapid assessment of regional sars-cov-2 community transmission through a convenience sample of healthcare workers, the netherlands key: cord-289684-rvbofsmb authors: fisher, jennifer; monette, derek l.; patel, krupa r.; kelley, brendan p.; kennedy, maura title: covid-19 associated parotitis: a case report date: 2020-06-27 journal: am j emerg med doi: 10.1016/j.ajem.2020.06.059 sha: doc_id: 289684 cord_uid: rvbofsmb as the 2019 coronavirus pandemic has unfolded, an increasing number of atypical presentations of covid-19 have been reported. as patients with covid-19 often present to emergency departments for initial care, it is important that emergency clinicians are familiar with these atypical presentations in order to prevent disease transmission. we present a case of a 21-year-old woman diagnosed in our ed with covid-19 associated parotitis and review the epidemiology and management of parotitis. we discuss the importance of considering covid-19 in the differential of parotitis and other viral-associated syndromes and emphasize the importance of donning personal protective equipment during the initial evaluation. the 2019 coronavirus pandemic presents healthcare workers (hcws) in the emergency department (ed) with numerous clinical and diagnostic challenges. currently, there are 6.6 million cases worldwide and 1.8 million cases in the united states (us) [1] . the most commonly reported symptoms include fever, dry cough, and fatigue [2] . however, an increasing number of asymptomatic infections and atypical presentations have been recognized, including gastrointestinal, neurological, and dermatologic complaints [2] [3] [4] . as patients with covid-19 often present first to eds for evaluation, it is critical ed clinicians are familiar with these atypical presentations in order to safely triage patients and prevent disease transmission. we present a case report of a woman infected with covid-19 and diagnosed with parotitis. a 21 year-old-female presented to the ed with left-sided facial and neck swelling. she presented to another ed eight days prior with fever, cough, and dyspnea and diagnosed with covid-19. despite improvement of her respiratory symptoms, she developed progressive unilateral facial and neck swelling causing subjective malocclusion and trismus. on review of systems, she reported decreased oral intake but denied persistent fevers, dental pain or facial weakness. on examination, the patient had normal vital signs and moderate left-sided cheek, preauricular, and submandibular swelling without erythema, induration or fluctuance. the intraoral exam was normal, with no purulent drainage expressible from stensen's duct and normal occlusion. the rest of her physical exam was unremarkable. imaging and blood laboratory values were obtained to work-up a differential that included infectious parotitis, sialolithiasis, salivary gland abscess, and neoplasm. laboratory values were notable for a leukopenia to 3,170/ul without lymphopenia. computed tomography (ct) of the neck demonstrated: diffuse asymmetric enlargement and swelling of the left parotid gland without an obstructing stone, mass, or abscess; periparotid inflammatory fat stranding; and free fluid extending into the left submandibular, submental, and parapharyngeal spaces and along the left sternocleidomastoid and strap muscles (figures 1 and 2) . otolaryngology was consulted given the extension of free fluid into surrounding anatomical spaces. her history, exam and ct findings were felt to be most consistent with uncomplicated acute infectious parotitis. her sensation of malocclusion was attributed to inflammation surrounding her muscles of mastication. the patient was prescribed a course of amoxicillin/clavulanate to j o u r n a l p r e -p r o o f treat a possible concomitant bacterial parotitis and advised to apply warm compresses, massage the gland, use sialagogues to increase salivary flow and stay hydrated. a variety of microorganisms can cause salivary gland infections and the parotid gland is most commonly affected [5, 6] . though paramyxovirus is the classic cause of viral parotitis, incidence of mumps has decreased 99% in the us due to widespread vaccination [5] . a variety of other respiratory viruses can lead to non-mumps parotitis, including enteroviruses and influenza, parainfluenza, coxsackie, and epstein-barr viruses [5, 6] . typically, viral parotitis is characterized by a prodrome of flu-like symptoms followed 2-4 days later by gradual swelling of the bilateral parotid glands, though unilateral involvement is seen in up to 25% of cases [6, 7] . acute suppurative parotitis is characterized by sudden onset of unilateral pain and swelling of the parotid gland [6, 7] . stasis of salivary flow secondary to dehydration is believed to facilitate bacterial migration into the parotid gland orifice and retrograde infection of the gland by oral flora [6, 7] . physical exam findings in suppurative parotitis include induration and tenderness of the parotid gland and purulent discharge from the duct orifice with massaging the gland [6, 7] . our patient had a mixed presentation. unilateral involvement and decreased oral intake favor a bacterial etiology; however, she did not have erythema or induration and her laboratory studies demonstrated leukopenia, not leukocytosis. while we believe this was a viral-induced parotitis, given the unilateral presentation we treated her for possible bacterial co-infection. at the time we evaluated this patient there were no reports of covid-19 associated parotitis. fortunately, our patient had already been diagnosed with covid-19, otherwise it is possible we may not have recognized facial swelling as a symptom of covid-19 and evaluated her without proper personal protection equipment (ppe). other cases of covid-19 parotitis and intraparotid lymphadenitis have recently been published [8, 9] . this adds to an expanding literature of atypical presentations of covid-19. the immune dysregulation and inflammation caused by covid-19 infection can affect numerous organs. guillian-barré syndrome (gbs) [10] and cutaneous small vessel vasculitis resulting in palpable purpuric toe lesions [11] have been reported in association with covid-19 infection . more recently, a multisystem inflammatory syndrome has been described in children infected with covid-19, causing a kawasaki-like illness associated with myocardial dysfunction and shock [12] . it is critical ed clinicians stay informed of the growing spectrum of clinical presentations of covid-19 to ensure appropriate clinical care and use of ppe to minimize disease transmission. j o u r n a l p r e -p r o o f clinical characteristics of 3,062 covid-19 patients: a meta-analysis neurologic manifestations of hospitalized patients with coronavirus disease cutaneous clinico-pathological findings in three covid-19-positive patients observed in the metropolitan area of salivary gland disorders viral mumps: increasing occurrences in the vaccinated population. oral surg oral med oral pathol oral radiol review of the major and minor salivary glands, part 1: anatomy, infectious, and inflammatory processes parotitis-like symptoms associated with covid-19 acute parotitis: a possible precocious clinical manifestation of sars-cov-2 infection? otolaryngol head neck surg guillain-barré syndrome associated with sars-cov-2 infection: causality or coincidence? cutaneous small vessel vasculitis secondary to covid-19 infection: a case report multisystem inflammatory syndrome in children during the covid-19 pandemic: a case series key: cord-264257-iu67n7qw authors: tsubokura, masaharu; nakada, haruka; matsumura, tomoko; kodama, yuko; kami, masahiro title: the impact of h1n1 influenza a virus pandemic on the emergency medical service in kobe date: 2010-02-12 journal: am j emerg med doi: 10.1016/j.ajem.2009.10.013 sha: doc_id: 264257 cord_uid: iu67n7qw nan to the editor, pandemic h1n1 2009 influenza virus infection has been identified as the cause of a widespread outbreak of febrile respiratory tract infection. on june 11, 2009 , the world health organization raised its pandemic alert to the highest level, phase 6. the h1n1 influenza virus infection rapidly spread all over japan after the first case was confirmed in kobe, japan, on may 16. the outbreak of this virus had a great impact on the japanese society. there was a shortage in masks and antiseptic [1, 2] . more than 4800 schools had been closed, medical services were swamped, many companies were forced into bankruptcy, and the stock market price declined [3, 4] . kobe suffered the most severe impact of the h1n1 influenza in japan. previous studies on severe acute respiratory syndrome [5] and the seasonal influenza [6] reported that emergency departments (eds) were overcrowded in the epidemic and that the number of ed ambulance diversion increased. emergency medical service (ems) was greatly influenced by the epidemic, whereas it remains unknown whether ems was influenced by the h1n1 influenza virus pandemic. in japan, the emergency paramedics are allowed to triage patients. when the emergency paramedics contact with patients, they negotiate with hospitalists to find a hospital where physicians can provide the medical support. to investigate the impacts of the h1n1 influenza pandemic on ems, we studied the situation of ems during the epidemic provided by the emergency paramedics. using an ambulance dispatch data of the fire prevention bureau of kobe, we extracted data on patients with fever higher than 37.5°c who called an ambulance between april 16 and june 16. we examined the following variables including the time between ems call and arrival at hospital, that between arrival to the site and the departure from it, and the number of times of negotiation by paramedics with hospitalists for patients' acceptance. to evaluate the impact of the pandemic on the ems system, we studied the longitudinal changes in these variables during the pandemic. we defined the period from april 16 to may 16 as the preepidemic stage and that from may 17 to june 16th as the postepidemic stage. we compared these variables in preepidemic stage with those in postepidemic stage. mann-whitney u test was used for statistical analysis, and p value of less than .05 was considered statistically significant. an ambulance was called by 961 patients during the study period, 469 and 492 patients in the preepidemic and postepidemic periods, respectively (fig. 1) . there was no significant difference between the 2 periods ( table 1) . the interval between ems call and arrival at hospital was significantly longer in the postepidemic period (mean, 28.8 minutes; range, 10.2-97.8 minutes) than in the preepidemic period (mean, 31.3 minutes; range, 9.4-128 minutes) (p b .001) ( fig. 2 and table 1 ). the number of hospitals with which the paramedics negotiated for patients' transfer was comparable between the 2 periods ( fig. 3 and table 1 ), whereas the sojourn time at the site was prolonged in the postepidemic period (mean, 17.0 minutes; range, 4.0-70 minutes) compared with the preepidemic period (mean, 14.0 minutes; range, 1.0fig. 1 the number of febrile patients who called an ambulance remained unchanged during the study period. 86 minutes). the difference was statistically significant (p b .001) ( fig. 4 and table 1 ). this study showed that h1n1 influenza pandemic did not have a great impact on the ems system of kobe. interestingly, the number of febrile patients who called an ambulance remained unchanged during the study period. this finding was in contrast to the situation in the eds and the clinics, which were overcrowded with patients who had been scared by the repetitive press reports. patients with h1n1 influenza occasionallydevelopedseveremanifestations.itisreasonableto assume that most patients with suspected h1n1 influenza infection might have visited clinic at its early stages on foot. it is interesting that paramedics needed an extra time of 3 minutes to triage patients. considering that the number of hospitals with which the paramedics negotiated for patients' transfer was comparable between the 2 periods, this extra time was required to provide the hospitalists with precise information on febrile patients, including symptoms and records of oversea travel. this finding is consistent with the fact that paramedics were required to fill in a form about patients' information during the study period. it is unlikely that hospitalists refused patients with possible h1n1 influenza infection because of fears of in-hospital spread of the infection. fig. 3 the number of hospitals with which the paramedics negotiated for patients' transfer was comparable between the 2 periods. fig. 2 the interval between ems call and arrival at hospital was significantly longer in the postepidemic period than in the preepidemic period. in response to …. we thank ⁎⁎⁎ for their insightful comments on our article concerning the diagnosis and management of preexcitation in the emergency department [1] . we would like to clarify the following points: atrial fibrillation can indeed present with an apparently regular rhythm and at rates that would seem concordant with simple reentrant tachycardia (approximately 150 beats/min). yet in the scenario presented by ⁎⁎⁎⁎, which attempts to differentiate atrial fibrillation with ventricular preexcitation from superventricular tachycardia with aberrant conduction in the bundle of his, the qrs complex configuration should readily differentiate the 2, at least in the classic case of aberrant conduction with left or right bundle branch blockade, and should not be a major concern (preexcitation should not give a bundle branch block morphology). the difficulty occurs then when one is not presented with a regular wide-complex tachycardia with a classic qrs complex morphology for bundle branch block. in this case, clinicians must strongly consider ventricular tachycardia (vt) in the differential diagnosis. fortunately, some guidance exists in this situation. steurer et al [2] studied this scenario and found that any of the following criteria identified vt (versus ventricular preexcitation) with a 75% fig. 4 the sojourn time at the site was prolonged in the postepidemic period compared with the preepidemic period. cooling methods used in the treatment of exertional heat illness heat stroke whole-body cooling of hyperthermic runners: comparison of two field therapies cooling methods for heatstroke victims a physiological body-cooling unit for treatment of heat stroke american college of sports medicine position stand. exertional heat illness during training and competition heat stroke: report on 18 cases the "golden hour" for heatstroke treatment emergency management of heat illness management of heat exhaustion in sydney's the sun city to surf fun runners survey and analysis of the medical experience for cax 8-80 sudden deaths in young competitive athletes: analysis of 1866 deaths in the united states early organ dysfunction course, cooling time and outcome in classic heatstroke cardiovascular and metabolic manifestations of heat stroke and severe heat exhaustion liver damage in heatstroke cardiac troponin t levels for risk stratification in acute ischemia cardiac fatigue after prolonged exercise spread of swine flu puts japan in crisis mode masks, gargles enjoying surge in popularity flu virus starts to take toll on businesses. travel industry seen facing biggest risk flu scare could harm economy. jpn times online effect of the sars outbreak on visits to a community hospital emergency department the impact of influenzaassociated respiratory illnesses on hospitalizations, physician visits, emergency room visits, and mortality this is a small-sized retrospective study, and unrecognized bias might have existed. nationwide survey will be necessary to evaluate the true impact of h1n1 influenza pandemic on ems system. however, it is likely that h1n1 influenza pandemic did not have a great impact on supply and demand of ems system. h5n1 influenza virus is another concern, although we should be careful in applying the results of this study to predicting its influence on the ems. there are considerable differences in the virulence between the 2 types of influenza viruses. key: cord-258676-6kgxpcwc authors: haleem, abid; javaid, mohd; vaishya, raju; deshmukh, s.g. title: areas of academic research with the impact of covid-19 date: 2020-04-15 journal: am j emerg med doi: 10.1016/j.ajem.2020.04.022 sha: doc_id: 258676 cord_uid: 6kgxpcwc coronavirus (covid-19) endemic is growing exponentially in the whole world. researchers, technologists, doctors and other healthcare workers are working day and night on the development of vaccine and medicinesto control and treat this virus. sars-cov-2 is the name of the virus responsible for causing covid-19 disease, which is highly infectious and lethal.with exponentially increasing infections, proportionate fatalities are being reported both from developed and under developed countries. as of today, more than one million people across the world have been reported infected with this virus, and more than 65,000 people have died of this disease. hence, there is an urgent requirement for conducting academic research on several aspects of this highly contagious disease, to find effective means of containment and treatment of the disease, for now, and in future. we have identified some opportunities for academic research related to covid-19 and have also provided suggestions to contain, prevent and treat this viral infection. the sars-cov-2 virus has significantly affected the health, economy, and socio-economic fabric of the global society. the costs involved in the containment and treatment of this infectious disease are exorbitantly high, which even the wealthiestand developed countries are finding it difficult to sustain. covid-19 pandemic has severely impacted the crude, stock market, gold and metals and almost all areas of the global market [1] . large research laboratories and corporate houses are working with a high speed to develop medicines and vaccines for the prevention and treatment of this dreaded disease. to deal with these current health management challenges, we need a comprehensive understanding of the effect on the health system, global business, and culture. covid-19 was declared a pandemic by the who on11th march 2020 [2] . covid-19 has become an international emergency in a short period and will have long-lasting effects. there is an urgent need to identify and study the areas of academic research which will be impacted by covid-19 [3] . this manuscript highlights potential areas of academic research which are likely to be impacted by covid-19. the main objectives of this paper are to provide awareness and to identify the research areas related to covid-19. it may help improve the understanding of this disease and describe the psychological impacts of this pandemic and how these could change as the disease spreads. it appears the coronavirus is zoonotic and originated in china. scientists have not yet been ableto identify the animal source of the infectious agent and have not determined whethera persistent animal reservoir of the infectious agent exists. it is also unclear whether sars, like influenza, is a seasonal disease that would have receded on its own. it remains to be seen whether it will reemerge on a seasonal basis, and if so, how virulent future manifestations would be. the answers to these questions would undoubtedly advance the world'sability to predict and prepare for a resurgence of covid-19. covid-19 has disrupted the economies and the lives of individuals around the world. there are many areas of research needed regarding covid-19 [5, 6] . table 1 identifies significant research areas which be profoundly impacted by this pandemic. we need to undertake extensive research on these areas. j o u r n a l p r e -p r o o f medication/ therapy  hydroxychloroquine and azithromycin have been claimed to be effective in prevention and treatment, in some anecdotal case series and in-vitro  certain retroviral drugs (used for the treatment of hiv) are being considered as a promising therapy  provide education of the disease and medication to ensure having the correct treatment  personal medication record, documentation and its action during medication are required 3 health care and equipment  research is going on for the essential medical equipment to fulfil the crisis of covid-19  various equipment like surgical masks, protective gear,sanitizer, andventilators must be available to all on time  there is a requirement of protective clothing which meets the required medical standards  test kit for this virus must be provided inaccurate time to avoid further delay 4 social  social distance should be maintained to avoid the further cause of infection and controlling of this disease  people gathering like a party, festival, and marriage must be avoided  social research must be establishedfor the knowledge and conducting a new inquiry  back to joint family systems  avoid cinema, gymnasiums, swimming pools and support clubs 5 economic  almost all manufacturing sectors are affected, and the whole supply chain is disrupted among all affected countries  travel & tourism industry  due to the closing of all market, business, and software companies, the economy is directly affected  mostly affected are the people who can earn their money at daily j o u r n a l p r e -p r o o f wages, lower middle class  research must be required on how to uplift the economy  poverty and hunger 6 environmental  overall air pollution is getting reduced by this virus which has a positive impact on the environment  climate change and industrialization  energy-efficient devices  lower carbon is required in future which can make less drasticchanges in manufacturing requirements 7 sustainability  fulfil the environmental, economic and social profit of the people  improve productivity and sustainable medical business and supply chain  sustainable supply chain, organizations, healthcare 8 psychiatric  covid-19 creates mental illness among the people who can further cause depression  to know how people can keep happy in their homes which can make better treatment of a mental disorder  work to handle the ongoing stress, situation and other psychosocial disabilities  proper positive communication and accurate information required among the people 9 the emergence of a new workplace and work culture  the proper new workplace is required to complete the ongoing work which can prevent to spread this virus  manage all meeting and events with proper precautions or better to conduct it online  audio, video conferencing, whatsapp group can be followed for discussion  avoid face to face meeting and successfully replace it with online events or teleconference to prevent any type of infection extensive research is required for the development of a vaccine for the prevention of coronavirus infection. there is an urgent need for early production and manufacturing of the essential items like personal protective equipment, medicines, and ventilators to combat this pandemic. all measures to keep a social distancing by the public must be ensured by avoiding social-cultural and religious programs and festivals etc. during this pandemic. along with these, healthcare measures to deal with covid-19 pandemic, there is also an imminent requirement for theresearch to improvethe global economy, which has taken a tremendous beating and is unlikely to recover in the near future [7, 8] . covid-19 pandemic is a public health emergency of international concern.it has posed new challenges to the global research community. with the help of academic research, there is a need for a better understanding of the covid-19 and its socio-economic ramifications on society. the future research will be multi-disciplinary and trans-national.we see a new wave of research in the biological and the medical sciences for the well-being of the civilization. timely research papers about covid-19 in china coronavirus has become a pandemic, who. says. 11 th preparedness and vulnerability of african countries against importations of covid-19: a modelling study learning from sars: preparing for the next disease outbreak: workshop summary breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of covid-19 associated pneumonia in clinical studies the effect of travel restrictions on the spread of the 2019 novel coronavirus (covid-19) outbreak can we contain the covid-19 outbreak with the same measures as for sars potential scenarios for the progression of a covid-19 epidemic in the european union and the european economic area none key: cord-333797-six8wzxz authors: heaney, ashley i.; griffin, gregory d.; simon, erin l. title: newly diagnosed diabetes and diabetic ketoacidosis precipitated by covid-19 infection date: 2020-06-06 journal: am j emerg med doi: 10.1016/j.ajem.2020.05.114 sha: doc_id: 333797 cord_uid: six8wzxz nan j o u r n a l p r e -p r o o f covid-19 infections and diabetes have been linked since early reports identified patients with diabetes mellitus having worse clinical outcomes. 1 infections have been shown to cause hyperglycemia in patients with known diabetes. 2 however, there has only been one case reported on covid-19 infection precipitating a new diagnosis of diabetes mellitus type ii. 3 we report a case of an individual without prior history of diabetes presenting in diabetic ketoacidosis after being diagnosed with covid-19 one week prior. a 54-year-old male presented to the emergency department (ed) via ems for worsening shortness of breath. patient reported a three-week history of fatigue and then developed shortness of breath and a cough one week prior to presentation. shortly after the patient's shortness of breath developed, the patient was tested as an outpatient for covid-19 and tested positive. the patient also endorsed loss of taste, lightheadedness and an intermittent cough. his past medical history is significant for hypertension, kidney stones, testicular hypofunction and erectile dysfunction. he had no prior surgeries, occasionally smoked cigars, and denied alcohol or drug use. his vital signs were blood pressure 143/87 mm/hg, heart rate 110 beats per minute, temperature 98.1f orally, respirations 26 breaths per minute, spo2 98% on room air. he had a bmi of 42.56 kg/m 2 . on physical exam he appeared ill and was tachycardic and tachypneic. his heart sounds were normal, his lungs clear to auscultation, abdomen was soft and nontender with normal bowel sounds, his legs revealed no swelling, and he had a normal neurological exam. the remainder of his physical examination was unremarkable. testing in the ed revealed hyperglycemia, anion gap metabolic acidosis and ketonuria which confirmed the patient to be in diabetic ketoacidosis (dka). he had a blood glucose of 463mg/dl, sodium of 126 mmol/l, potassium of 5.5mmol/l, chloride of 86mmol/l, and co2 of 9mmol/l, creatinine of 1.24 mg/dl and an anion gap of 31. his wbc were 9.3 thou/cmm, with absolute neutrophils of 7.56 thou/cmm. the remainder of his cbc differential was normal. his venous ph was 7.193, pco2 was 26.9 mm hg, hco3 was 9.9mmol/l with a base excess of -17.3meq/l and lactic acid was 3.8meq/l. hepatic function revealed an alt of 66u/dl and the remainder was unremarkable. rapid covid-19 testing was positive. urinalysis revealed >1000 mg/dl of glucose, >160 mg/dl ketones and 30 mg/dl of protein. his chest x-ray did not show any infiltrates or other abnormalities. while in the ed he was treated with 2 liters of normal saline and an insulin drip was started at 0.1unit/kg of ideal body weight/hour. the patient was admitted to the medical intensive care unit. further lab testing revealed an elevated ferritin 1763ng/ml, his d-dimer was normal at 410 ng/ml, c-reactive protein 3.6 mg/dl, lactate dehydrogenase was 228 u/l. while admitted, the patient's acidosis resolved and he was transitioned to subcutaneous insulin and a diabetic diet. he was discharged to home on hospital day 5. there is a paucity of data on diabetic ketoacidosis (dka) and covid-19 infection. we report a case of dka precipitated by covid-19 in a patient with newly diagnosed diabetes mellitus. there has been one prior case report of dka and new onset diabetes mellitus in the setting of covid-19 infection. 3 dka occurs as a result of insulin deficiency, increased counterregulatory response which results in the production of ketones. the angiotensin-converting enzyme 2 (ace2) is a key enzyme in the renin-angiotensin-aldosterone system and it catalyzed the j o u r n a l p r e -p r o o f conversion of angiotensin ii to angiotensin. 4 ace2 is found in the lungs, pancreas and serves as the entry point for covid-19. 4 once endocytosis of the virus complex occurs, ace2 expression is downregulated. 5 this allows for entry of covid-19 into pancreatic islet cells which may cause beta cell injury. 6 the downregulation of ace2 can also lead to unopposed angiotensin ii, which may impede insulin secretion. 7 these factors may have played a role in precipitating dka in this patient. as emergency physicians continue to treat patients with covid-19 infection, it is important to understand the implications this disease can have on organ systems. further studies and reports will help to delineate the exact pathophysiology. patients with elevated blood sugar and no history of diabetes should be evaluated for the possibility of new onset diabetes mellitus and dka, especially in the setting of concomitant covid-19 infection. covid-19 infection may cause ketosis and ketoacidosis practical recommendations for the management of diabetes in patients with covid-19 diabetic ketoacidosis precipitated by covid-19 in a patient with newly diagnosed diabetes mellitus endocrine and metabolic link to coronavirus infection renin-angiotensin-aldosterone system inhibitors in patients with covid-19 binding of sars coronavirus to its receptor damages islets and causes acute diabetes angiotensin ii and the endocrine pancreas: effects on islet blood flow and insulin secretion in rats key: cord-293535-9bj5ev1a authors: wang, yushu; ao, guangyu; qi, xin; zeng, jian title: the influence of corticosteroid on patients with covid-19 infection: a meta-analysis date: 2020-06-23 journal: am j emerg med doi: 10.1016/j.ajem.2020.06.040 sha: doc_id: 293535 cord_uid: 9bj5ev1a nan j o u r n a l p r e -p r o o f (sars-cov) and middle eastern respiratory syndrome (mers)-cov and did not investigate the effect of corticosteroids on mortality in covid-19 patients. with an increased number of covid-19 literature now published, it has enabled a more robust and profound analysis of current data which is urgently needed by the international medical and scientific communities. therefore, we aim to perform this meta-analysis to identify the roles of corticosteroids in patients with or without severe covid-19. an electronic search was performed in pubmed, embase, cochrane library, and china national knowledge infrastructure (cnki), using the keywords "steroid" or "corticosteroid" or "cortisol" or "prednisolone" or "prednisone" or "glucocorticoid" or "hydrocortisone" or "dexamethasone" or "methylprednisolone" and "novel coronavirus" or "2019-ncov" or "covid-19" or "sars-cov-2" between 2019 and present time (i.e., up to may 7th, 2020) and without language restrictions. the inclusion criteria for studies were as follows: (1) studies comparing the use of corticosteroids between severe and non-severe covid-19 patients; (2) patients must be diagnosed with covid-19 infection and (3) abstracts, case reports, review articles, editorials or letters were excluded. the title, abstract and full text of all documents identified according to these search criteria were assessed independently by two reviewers (y.w. and g.a.). a meta-analysis was then carried out for calculating the individual and pooled risk ratios (rr) with their relative 95% confidence interval (95% ci), using revman 5.3 (cochrane collaboration). heterogeneity among studies was evaluated using cochran's q test and the i 2 statistic, with an i 2 less than 25%, 25% to j o u r n a l p r e -p r o o f 50%, and greater than 50% corresponding to low, moderate, and high heterogeneity, respectively. p < 0.05 was considered statistically significant. a total of 466 studies were originally identified based on our search criteria, 411 of which were excluded after title, abstract or full text reading since they were review articles, editorial materials or letters, and did not report the use of corticosteroid in patients with or without severe covid-19. thus, 16 studies were finally included in our meta-analysis [5-20]. the study population ranged from 30 to 1,099. the details of each included study are shown in table 1 . the pooled rr of these studies is presented in figure 1 . although the heterogeneity was considerably high (i.e., i 2 , 88%; p ＜ 0.00001), severe patients were found to be more likely to require corticosteroids therapy (rr = 2.11, 95%ci = 1.53-2.92, p ＜ 0.00001). in addition, no statistically which lessons shall we learn from the 2019 novel coronavirus outbreak? clinical features and treatment of covid-19 patients in northeast chongqing risk factors for severity and mortality in adult covid-19 inpatients in wuhan clinical manifestations and sero-immunological characteristics of 155 patients with covid-19 analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease correction to: clinical predictors of mortality due to covid-19 based on an analysis of data of 150 patients from key: cord-265098-u5qssib9 authors: fu, xin-yan; shen, xiang-feng; cheng, yong-ran; zhou, meng-yun; ye, lan; feng, zhan-hui; xu, zhao; chen, juan; wang, ming-wei; zhang, xing-wei title: effect of covid-19 outbreak on the treatment time of patients with acute st-segment elevation myocardial infarction date: 2020-09-17 journal: am j emerg med doi: 10.1016/j.ajem.2020.09.038 sha: doc_id: 265098 cord_uid: u5qssib9 objective: to explore the effect of covid-19 outbreak on the treatment time of patients with st-segment elevation myocardial infarction (stemi) in hangzhou, china. methods: we retrospectively reviewed the data of stemi patients admitted to the hangzhou chest pain center (cpc) during a covid-19 epidemic period in 2020 (24 cases) and the same period in 2019 (29 cases). general characteristics of the patients were recorded, analyzed, and compared. moreover, we compared the groups for the time from symptom onset to the first medical contact (so-to-fmc), time from first medical contact to balloon expansion (fmc-to-b), time from hospital door entry to first balloon expansion (d-to-b), and catheter room activation time. the groups were also compared for postoperative cardiac color doppler ultrasonographic left ventricular ejection fraction (lvef),the incidence of major adverse cardiovascular and cerebrovascular events (macce),kaplan-meier survival curves during the 28 days after the operation. results: the times of so-to-fmc, d-to-b, and catheter room activation in the 2020 group were significantly longer than those in the 2019 group (p < 0.05). the cumulative mortality after the surgery in the 2020 group was significantly higher than the 2019 group (p < 0.05). conclusion: the pre-hospital and in-hospital treatment times of stemi patients during the covid-19 epidemic were longer than those before the epidemic. cumulative mortality was showed in kaplan-meier survival curves after the surgery in the 2020 group was significantly different higher than the 2019 group during the 28 days.the diagnosis and treatment process of stemi patients during an epidemic should be optimized to improve their prognosis. multiple cases of pneumonia patients, infected with a novel coronavirus (sars-cov-2), were discovered in wuhan city, hubei, china, since december 2019. [1, 2] with the spread of the epidemic, confirmed cases were found in other provinces in china and most countries around the world. as of may 10, 2020, there were 3,917,366 confirmed cases worldwide, and 274,361 deaths, far exceeding the number of people affected by atypical pneumonia or the middle east respiratory syndrome (mers). [3, 4] the national health commission of china quickly announced the disease as a class b infectious disease, as stipulated in the chinese law on the prevention and control of infectious diseases. it also required the activation of preventive and control measures of class a infectious diseases. [5] on january 23, 2020, the closure of wuhan city was announced. before this, on january 20, 2020, the hangzhou chest pain center (cpc) has formulated a procedure for patient consultation under the preventive and control measures of covid-19 ( figure 1 ). the epidemic occurred during the transition from winter to spring, a ( figure 2 ), striving to prevent and control the epidemic while optimizing the treatment. this action followed the stemi merger strategy for the management of sars-cov-2 infection in the people's hospital of wuhan university. [8] as part of the improved cooperation with the hospital, we carried out fever diagnoses and disease treatment. however, we hypothesized that the covid-19 epidemic might have interfered with diagnosing and treating acute myocardial infarction. to clarify this issue, we performed a retrospective study comparing stemi patients at the hangzhou cpc during the covid-19 epidemic (january 20 to april 20, 2020) with those during the corresponding period in 2019. we aimed to explore the impact of covid-19 on the treatment time of stemi patients and provide a solid base in support of standardizing the treatment process of stemi patients during an epidemic situation such as covid-19. clinical data of stemi patients who visited the hangzhou cpc were collected. macce events included non-fatal myocardial infarction, cardiac death, target vessel revascularization, and stroke. cardiac death refers to death due to myocardial ischemia, leading to cardiac arrest before the loss of other functions; target vessel revascularization refers to lesions in the original stent area and the coronary arteries within 5 mm from both ends of such stent. it also includes lesions in the area outside the target lesion, located in the main branch corresponding to the revascularized coronary artery; stroke refers to cerebral hemorrhage or cerebral infarction. [10] this study was approved by the human study ethics committee of the affiliated hospital of hangzhou normal university. data analysis was performed using the r program (v3.60). an independent sample t-test was used for group comparisons. the kaplan-meier survival curve was used to estimate the survival rate. wilcoxon signed-rank test was used to compare the j o u r n a l p r e -p r o o f journal pre-proof survival rate between the two groups. continuous variables are presented as mean ± standard deviation. differences with p < 0.05 were considered statistically significant. a total of 24 patients in the 2020 group and 29 patients in the 2019 group were showed in table 1 . the baseline data and risk factors relating to coronary heart disease were analyzed in both groups.there were no statistical significance in terms of age,sex,drinking history, smoking history, hypertension, diabetes, hypercholesterolemia, obesity, and family history of coronary heart disease in the two groups. with one patient in each group having a history of myocardial infarction, the difference was insignificant. the groups also did not differ in the myocardial infarction location, killip classification, and lvef. based on these results, we think that the reasons for the delay in stemi treatment times can be summarized along the following lines. first, patients delayed their visit to the hospital because they feared becoming infected with sars-cov-2. this delay resulted in a significant prolongation of the so-to-fmc time. during the epidemic, ordinary patients with non-emergency cardiovascular diseases were advised to avoid hospital admission as much as possible. after the epidemic was contained, they were admitted to the hospital for treatment. the patients, especially the elderly, often cannot distinguish between emergency and non-emergency events. moreover, the patients were extremely anxious about the spread of covid-19, so they delayed seeking medical help, and attempted to relieve the chest pain symptoms by taking quick-acting rescue pills or other drugs. these patients did not call for help until it was already intolerable. second, after the patients have arrived at the hospital gates, the fmc-to-ecg and d-to-b times were further prolonged because of the covid-19 screening of the patient and the accompanying family members during the epidemic. clinical features of patients infected with 2019 novel coronavirus in wuhan a rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-ncov) infected pneumonia (standard version) the epidemic of 2019-novel-coronavirus j o u r n a l p r e -p r o o f journal pre-proof (2019-ncov) pneumonia and insights for emerging infectious diseases in the future coronavirus disease (covid-2019) situation reports interpretation of "guidelines for the diagnosis and treatment of novel coronavirus (2019-ncov) infection by the national health commission (trial version5) summary of "chinese cardiovascular disease report patient and system delays in the treatment of acute coronary syndrome suggestions on management strategies for st-segment elevation acute myocardial infarction (stemi) combined with novel coronavirus infection impact of symptom onset to first medical contact time on the prognosis of patients with acute st-segment elevation myocardial infarction association of gender with clinical outcomes of patients with acute st-segment elevation myocardial infarction presenting with acute heart failure. coron artery dis protocol of the china st-segment elevation myocardial infarction (stemi) care project (cscap): a 10-year project to improve quality of care by building up a regional stemi care network st-segment elevation myocardial infarction effects of target value management for quality control indexes in chest pain center on efficiency and effectiveness of in-hospital treatment for stemi patients key: cord-286348-3p7gz8wi authors: choudhary, rahul; sharma, jai bharat; deora, surender; kaushik, atul; sanghvi, sanjeev; mathur, rohit title: impact of covid-19 outbreak on clinical presentation of patients admitted for acute heart failure in india date: 2020-10-16 journal: am j emerg med doi: 10.1016/j.ajem.2020.10.025 sha: doc_id: 286348 cord_uid: 3p7gz8wi acute heart failure (ahf) is a life-threatening, rapid onset or worsening of sign and/or symptoms of heart failure (hf) which often requires urgent hospitalization for rapid evaluation and treatment. it may present as de novo or, more frequently, as a result of acute decompensation of chronic heart failure (adhf). apart from the economic burden on patient and health care system, each ahf related hospitalization is associated with significant increases in 12-month rehospitalization and mortality rate (44% and 17% in esc-hf pilot study; 30.2 and 30.8% in trivandrum heart failure registry) maggioni et al. (2013), harikrishnan et al. (2017) [1,2]. as of july 15th, india has about 936,181 cases and nearly 24,309 death attributed to novel coronavirus disease 2019 (covid-19) infection (solomon et al., n.d. [3]). unprecedented apprehension due to the rapid spread of covid-19 pandemic has resulted in hospital avoiding behavior among patients suffering other diseases, including hf. also, spread of covid-19 pandemic attracted the major allocation of healthcare infrastructure and human resources, including emergency services, for the care of covid-19 infected patients, and little is known about the effect of this stressed-out healthcare system on short and long term outcome in patients suffering from hf. although, the implementation of lockdown by the government (from march 25, 2020) initially slowed the community spread of covid-19, but inadvertently, suspension of public transport further affected the delivery of medical care for hf patients, as most of the patients in india still use public transport for their emergency department (ed) visits. in this study, we performed a retrospective analysis of all consecutive patients who were admitted for ahf (de novo and adhf; left ventricular ejection fraction <40%) in two medical college hospitals providing healthcare services in jodhpur, western india. both are regional tertiary care centres of local hub and spike networks for the management of various cardiovascular emergencies. our eds have a separate registration desks for patients coming with non-covid-19 emergencies and covid-19 symptoms, with clear signs at the entrance directing patients to the designated registration desk. also, ed was expanded to avoid overcrowding and separate waiting area was created for those who have covid-19 signs and symptoms. we analysed demographic, clinical, echocardiographic and outcome parameters in patients admitted for ahf during the study period of 16 weeks (march 25 to july 14, 2020; starting from the day when lockdown was imposed by government of india) and compared this data with a control period of 16 weeks (dec 05, 2019 to march 24, 2020; when there was no lockdown and number of covid-19 attributed death ≤10). in addition, hospitalization rates during the study period were also compared with data from the same period in 2018–19. patients diagnosed with severe acute respiratory syndrome coronavirus 2 (sars-cov-2) were not included in study. our analysis of patients admitted during the study (lockdown) period revealed 69% reduction in ahf hospitalizations as compared to the control period (241 vs 782) and 60% reduction compared to same calendar period from the previous year (144 vs 602; figure 1). it was contrary to an expected increase due to the availability issue of guideline-directed medical therapy in follow-up patients and an anticipated surge in ahf due to late presentation of patients with acute myocardial infarction associated mechanical complications. among the patients from the lockdown period, 96.7% presented with nyha iv symptoms, this was significantly higher than the rate during the control period (out of 782; 76.6% presented with nyha iv symptoms during the control period; p value <0.001; table 1). the mean age (±sd) of patients in study and control period was 63.5(±11.2) and 61.1(±11.9) respectively, with no significant difference. compared with control group, study group patients were more commonly male (82.6 vs 71.6%; p value <0.02), more likely to have atrial fibrillation (23.7 vs 18.2%; p value <0.02), lower egfr (64.6 vs 77.7%; p value <0.05), lower mean ejection fraction (24.2 ± 5.6 vs 30.4 ± 4.9%; p value <0.001) and higher nt pro bnp levels (mean value 7349.2 vs 5680.4 pg/ml; p value <0.001). median length of stay during study and control period was 5 and 4 days respectively. we also observed significantly increased in-hospital mortality during the lockdown period as compared to the control period (8.3% vs 5.4%; p value <0.001). the number of patients presenting to ed with ahf in western india has reduced significantly, and yet, late presentations with advanced symptoms and low ef seem to have increased. similar pattern of decreased admission for cardiovascular emergency was reported from california, where weekly rates of hospitalization for acute myocardial infarction decreased by up to 48% during the covid-19 period (solomon et al., n.d. [3]). the current case fatality rate for covid-19 in india is approximately 2.6% [4], which is far less than that of ahf and we presume that many untreated ahf patients must have died at home during covid-19 pandemic. there have been reports of the inexplicable increase in out of hospital cardiac arrests, revealing that patients were staying too long at home to seek care for a more severe medical condition (wong et al., 2020 [5]). complete suspension of public transit system along with lack of emergency medical services in india, risk of acquiring covid-19 at ed and misleading information in media and social platforms about flooding of hospital beds due to covid-19, even when there were reserved wards for other emergencies, led to hospital avoiding behavior among patients suffering from even the most serious medical conditions. hospitals are now erroneously perceived as reservoirs of sars-cov-2. community educational campaigns are imperative to convey that hospitals are secured, resourceful, and fully prepared for life-threatening emergencies; which if untreated, has higher morbidity and mortality rate as compared to covid-19. in this study, we performed a retrospective analysis of all consecutive patients who were admitted for ahf (de novo and adhf; left ventricular ejection fraction <40%) in two medical college hospitals providing healthcare services in jodhpur, western india. both are regional tertiary care centres of local hub and spike networks for the management of various cardiovascular emergencies. our eds have a separate registration desks for patients coming with non-covid-19 emergencies and covid-19 symptoms, with clear signs at the entrance directing patients to the designated registration desk. also, ed was expanded to avoid overcrowding and separate waiting area was created for those who have covid-19 signs and symptoms. we analysed demographic, clinical, echocardiographic and outcome parameters in patients admitted for ahf during the study period of 16 weeks (march 25 to july 14, 2020; starting from the day when lockdown was imposed by government of india) and compared this data with a control period of 16 weeks (dec 05, 2019 to march 24, 2020; when there was no lockdown and number of covid-19 attributed death ≤10). in addition, hospitalization rates during the study period were also compared with data from the same period in 2018-19. patients diagnosed with severe acute respiratory syndrome coronavirus 2 (sars-cov-2) were not included in study. our analysis of patients admitted during the study (lockdown) period revealed 69% reduction in ahf hospitalizations as compared to the control period (241 vs 782) and 60% reduction compared to same calendar period from the previous year (144 vs 602; figure 1 ). it was contrary to an expected increase due to the availability issue of guideline-directed medical therapy in follow-up patients and an anticipated surge in ahf due to late presentation of patients with acute myocardial infarction associated mechanical complications. among the patients from the lockdown period, 96.7% presented with nyha iv symptoms, this was significantly higher than the rate during the control period (out of 782; 76.6% presented with j o u r n a l p r e -p r o o f journal pre-proof nyha iv symptoms during the control period; p value <0.001; table 1 ). the mean age (±sd) of patients in study and control period was 63.5(±11.2) and 61.1(±11.9) respectively, with no significant difference. compared with control group, study group patients were more commonly male (82.6 vs 71.6%; p value <0.02), more likely to have atrial fibrillation (23.7 vs 18.2%; p value <0.02), lower egfr (64.6 vs 77.7%; p value <0.05), lower mean ejection fraction (24.2±5.6 vs 30.4 ±4.9 %; p value <0.001) and higher nt pro bnp levels (mean value 7349.2 vs 5680.4 pg/ml; p value <0.001). median length of stay during study and control period was 5 and 4 days respectively. we also observed significantly increased inhospital mortality during the lockdown period as compared to the control period (8.3% vs 5.4%; p value <0.001). the number of patients presenting to ed with ahf in western india has reduced significantly, and yet, late presentations with advanced symptoms and low ef seem to have increased. similar pattern of decreased admission for cardiovascular emergency was reported from california, where weekly rates of hospitalization for acute myocardial infarction decreased by up to 48% during the covid-19 period. 3 the current case fatality rate for covid-19 in india is approximately 2.6%, 4 which is far less than that of ahf and we presume that many untreated ahf patients must have died at home during covid-19 pandemic. there have been reports of the inexplicable increase in out of hospital cardiac arrests, revealing that patients were staying too long at home to seek care for a more severe medical condition. 5 complete suspension of public transit system along with lack of emergency medical services in india, risk of acquiring covid-19 at ed and misleading information in media and social platforms about flooding of hospital beds due to covid-19, even when there were reserved wards for other emergencies, led to hospital avoiding behavior among patients suffering from even the most serious medical conditions. hospitals are now erroneously perceived as j o u r n a l p r e -p r o o f reservoirs of sars-cov-2. community educational campaigns are imperative to convey that hospitals are secured, resourceful, and fully prepared for life-threatening emergencies; which if untreated, has higher morbidity and mortality rate as compared to covid-19. keywords: acute heart failure; covid-19; cardiovascular emergencies. eurobservational research programme: regional differences and 1-year follow-up results of the heart failure pilot survey (esc-hf pilot) one-year mortality outcomes and hospital readmissions of patients admitted with acute heart failure: data from the trivandrum heart failure registry in kerala, india the covid-19 pandemic and the incidence of acute myocardial infarction where are all the patients? addressing covid-19 fear to encourage sick patients to seek emergency care figure 1. hospitalization for ahf before and during the lockdown for covid-19 pandemic in 2019-20 and during the same period lockdown was imposed on march 25, 2020; right half of figure (shaded part) shows the lockdown period. the data shown in blue are weekly admissions for acute heart failure (ahf) during period from key: cord-310207-lfub6y5m authors: nanda, satyan; handa, rahul; prasad, atul; anand, rajiv; zutshi, dhruv; dass, sujata k.; bedi, prabhjeet kaur; pahuja, aarti; shah, pankaj kumar; sharma, bipan title: covid-19 associated guillain-barre syndrome: contrasting tale of four patients from a tertiary care centre in india date: 2020-09-16 journal: am j emerg med doi: 10.1016/j.ajem.2020.09.029 sha: doc_id: 310207 cord_uid: lfub6y5m background: globally, more than 12 million people have been infected with covid −19 infection till date with more than 500,000 fatalities. although, covid-19 commonly presents with marked respiratory symptoms in the form of cough and dyspnoea, a neurotropic presentation has been described of late as well. objective: in this brief communication we report four cases of covid-19 who presented to our hospital with features suggestive of guillain-barre syndrome (gbs). discussion: the mechanisms by which sars-cov-2 causes neurologic damage are multifaceted, including direct damage to specific receptors, cytokine-related injury, secondary hypoxia, and retrograde travel along nerve fibres. the pathogenesis of gbs secondary to covid-19 is not well understood. it is hypothesised that viral illnesses related gbs could be due to autoantibodies or direct neurotoxic effects of viruses. conclusion: nervous system involvement in covid-19 may have been grossly underestimated. in this era of pandemic, it is very important for the physicians to be aware of association of gbs with covid-19, as early diagnosis and treatment of this complication could have gratifying results. to the best of our knowledge, this is the first such case series of guillain-barre syndrome associated with covid-19 to be reported from india. described of late as well [3] . guillain barre syndrome (gbs) is best described as an acute inflammatory polyradiculoneuropathy clinically characterised by areflexia and progressive weakness of arms and legs. though, many rare variants of gbs have been described, the commonly observed subtypes such as acute motor axonal neuropathy (aman), acute motor sensory axonal neuropathy (amsan) and acute inflammatory demyelinating polyradiculoneuropathy (aidp) tend to fulfil the above-mentioned criteria [4] . in this brief communication we report four cases of covid-19 who presented to our hospital with features suggestive of gbs. a 55-year-old female with background history of diabetes mellitus, hypertension and cholelithiasis presented with chief complaints of fever 10 days back lasting for 3 days, pain abdomen for 5 days; acute onset rapidly progressive symmetric weakness of all four limbs for 3 days (lower limbs followed by upper limbs). there was no history suggestive of cranial nerve, bowel or bladder involvement. on examination, patient was hemodynamically stable with 98% oxygen saturation (spo2) on room air. cranial nerve examination was normal. motor examination revealed generalised hypotonia, grade table 2 ]. after informed consent the patient was started on j o u r n a l p r e -p r o o f iv immunoglobulin (ivig): 0.4 g/kg body weight per day for five days. in view of a possibility of covid-19 associated hypercoagulable state (elevated d dimer) she was also given therapeutic anticoagulation. there was no further progression of her symptoms after starting ivig and the patient was discharged after 10 days of hospital stay with grade 4/5 power in both lower limbs and grade 4+/5 power in both upper limbs. a 72-year-old male, known case of hypertension for 5 years on treatment, presented to the emergency department of our hospital with chief complaints of fever 6 days back lasting for 2 days, cough since past 3 days associated with progressive weakness of all four limbs since past 2 days. he had lost the ability to walk independently since 1 day. there was no history suggestive of cranial nerve involvement, diarrhoea, bowel and bladder symptoms, or dog bite. on examination, patient was hemodynamically stable and afebrile. neurological examination revealed no cranial nerve involvement. motor examination showed generalised hypotonia, grade 2/5 power in both lower limbs and grade 3/5 in both upper limbs as per mrc grading. deep tendon reflexes were universally absent and plantar response was flexor bilaterally. the sensory examination was normal. his sbc was 12. his routine blood investigations including complete blood count, serum sodium and potassium, liver and kidney function tests were normal. viral markers including human immunodeficiency virus, hepatitis b surface antigen (hbsag) and hepatitis c virus (hcv) antibody were negative. serum b12 levels and thyroid function tests were normal. covid-19 testing was positive by rt-pcr technique. contrast mri of whole spine was suggestive of degenerative changes in the spine [ table 2 ]. csf examination showed albumino-cytological dissociation and inflammatory markers were elevated [ table 1 limbs. contrast mri of whole spine showed mild degenerative changes of the spine [ table 2 ]. csf examination showed albumino-cytological dissociation with mildly elevated inflammatory markers in the blood [ table 1 and 2]. chest x-ray showed evidence of bilateral lower and midzone infiltrates. ivig was given at 0.4gm/kg body weight/day for 5 days with other supportive treatment. good neurological improvement was observed over the next 5 days and patient was discharged after 7 days. at the time of discharge patient had 4+/5 power in both lower limbs with mild residual facial palsy. a member of the beta-coronaviridae family, sars-cov-2 is an enveloped, non-segmented, single-stranded, positive-sense rna virus. the mechanisms by which sars-cov-2 causes neurologic damage are multifaceted, including direct damage to specific receptors, cytokinerelated injury, secondary hypoxia, and retrograde travel along nerve fibres [5] . three of the above cases presented with neurological complaints and had no respiratory features secondary to covid-19, and these were the ones who did quite well with treatment. one patient who presented with respiratory complaints and x-ray changes along with neurological deficits continued to deteriorate even after starting treatment for both gbs and covid-19, and eventually succumbed to the disease. in the past gbs has been associated with a number of viral infections, most recently to zika virus [6] . the pathogenesis of gbs secondary to covid-19 is not well understood. it is well documented that the cross immunity which plays an important role in gbs secondary to bacterial infections such as c. jejuni may not be the main reason behind gbs associated with viral infections namely dengue and zika. it is hypothesised that viral illnesses related gbs could be due to autoantibodies or direct neurotoxic effects of viruses [7] . although, our patients had symptoms. this was in contrast to typical gbs, wherein cranial nerve involvement is quite common. less frequent involvement of cranial nerves in gbs secondary to covid-19 is also in contrast to zika virus associated gbs, where facial and third nerve involvement was quite common [7] . all the above patients had significantly raised pro-inflammatory markers that might suggest a causal link to pro-inflammatory state secondary to covid-19. similar rise in inflammatory markers were noted in other case reports as well, and it was hypothesised that these inflammatory mediators and cytokines may play a role in triggering an immune mediated neuropathy [8] . all our patients developed features of gbs, 5-10 days after the onset of covid-19 symptoms, which is similar to the interval seen with guillain-barré syndrome that occurs secondary to other infections [9] . most of the previous case reports documented a similar interval duration between the onset of covid-19 symptoms and gbs [2, 9] . three of our patients had an excellent response to ivig and were ambulatory without support within 10 days of starting treatment. previous case reports show mixed treatment response with some reporting very good recovery, while others coronavirus disease c d-: situation report covid-19 and guillain-barre syndrome: a systematic review of case reports neurologic manifestations of hospitalized patients with coronavirus disease guillain-barré syndrome and related disorders neurologic complications of covid-19 guillain-barré syndrome associated with sars-cov-2 infection is covid-19-related guillain-barré syndrome different atypical clinical presentation of covid-19: a case of guillain-barrè syndrome related to sars-cov-2 infection guillain-barré syndrome associated with sars-cov-2 key: cord-312623-ktswh3fu authors: werthman-ehrenreich, amanda title: mucormycosis with orbital compartment syndrome in a patient with covid-19 date: 2020-09-16 journal: am j emerg med doi: 10.1016/j.ajem.2020.09.032 sha: doc_id: 312623 cord_uid: ktswh3fu abstract during the current pandemic of covid-19, a myriad of manifestations and complications has emerged and are being reported on. we are discovering patients with covid-19 are at increased risk of acute cardiac injury, arrythmias, thromboembolic complications (pulmonary embolism and acute stroke), and secondary infection to name a few. i describe a novel case of covid-19 in a previously healthy 33-year-old female who presented for altered mental status and proptosis. she was ultimately diagnosed with mucormycosis and orbital compartment syndrome, in addition to covid-19. early identification of these high morbidity conditions is key to allow for optimal treatment and improved outcomes. during the current pandemic of covid-19, a myriad of manifestations and complications has emerged and are being reported on. we are discovering patients with covid-19 are at increased risk of acute cardiac injury, arrythmias, thromboembolic complications (pulmonary embolism and acute stroke), and secondary infection to name a few. i describe a novel case of covid-19 in a previously healthy 33-year-old female who presented for altered mental status and proptosis. she was ultimately diagnosed with mucormycosis and orbital compartment syndrome, in addition to covid-19. early identification of these high morbidity conditions is key to allow for optimal treatment and improved outcomes. keywords: covid-19, mucormycosis, orbital compartment syndrome coronavirus disease 2019 (covid-19) is a new disease entity caused by a novel coronavirus (sars-cov-2) first documented in china in december 2019 and subsequently causing a worldwide pandemic. while the pathophysiology of the virus is still under investigation, new symptomatic manifestations and complications of the disease continue to be identified and described in medical literature. mucormycosis and orbital compartment syndrome are rare, time sensitive conditions that must be recognized and treated promptly to avoid mortality and morbidity. herein i present a case of rhino-orbital-cerebral mucormycosis in a patient who presented to the emergency department with altered mental status, proptosis, and covid-19 infection. a 33-year-old somali female with past medical history of hypertension and asthma, presented to the emergency department with altered mental status. her husband stated the patient began with symptoms of vomiting, cough, and shortness of breath 2 days prior to presentation. vital signs on arrival were notable for mild tachycardia, hypertension, and tachypnea. she was afebrile and maintained normal oxygen saturation. upon examination, she appeared in moderate distress with acutely altered mental status. most notable was left eye ptosis with 1 cm proptosis. the eye had a fixed dilated pupil with complete ophthalmoplegia. no surrounding erythema, warmth or discharge was noted. her nasal exam was unremarkable. the mucous membranes were dry, and palate had brown, dry appearing secretions. emergency management: blood chemistry, complete blood count, lactate, blood gas, and blood cultures were obtained. the patient was found to have a white blood cell count of 27 with 82.9% neutrophils and 5.1% lymphocytes. serum chemistry was significant for glucose 649, carbon dioxide 5, creatinine 2.28, and lactate 2.8. venous blood gas found a ph < 6.9, and pco 2 29. the chest radiograph showed left lower lobe consolidation consistent with pneumonia (figure 1). a stat ct of the head, face, and orbits were obtained. ct head was negative for acute pathology. the face ct j o u r n a l p r e -p r o o f face showed significant for moderate bilateral maxillary sinus mucosal thickening as well as ethmoid sinus mucosal thickening, and mucosal opacification of the ostiomeatal units (figure 2). emergent lateral canthotomy was performed by the ed physician due to intraocular pressures of 80mmhg in the setting of proptosis and ophthalmoplegia. otolaryngology was consulted and the nasal mucosa was swabbed for culture. ophthalmology was also consulted, and the patient was admitted to the medical intensive care unit. the patient's dka was treated with intravenous fluids, sodium bicarbonate and, insulin infusions per local protocol. vancomycin and piperacillin-tazobactam were administered for severe sepsis in treatment of pneumonia and possible orbital cellulitis. amphotericin b was added for coverage of possible mucormycosis. otolaryngology took the patient to the operating room for sinus debridement. intraoperatively, the left middle turbinate was noted to be black. sinus cultures were positive for moderate staphylococcus aureus, as well as extensive fungal elements, including hyphae, yeast. the fungal culture was consistent with mucormycosis. an mri brain was obtained during the icu stay, demonstrating extensive multifocal signal abnormality with edema, and evidence of ischemia and infarction ( figure 3 and 4) . these findings were highly suspicious for invasive rhino-orbital-cerebral mucormycosis. mra head and neck was unremarkable. in addition, the patient received remdesivir and convalescent plasma. on day 24 of hospitalization, repeat mri of the brain showed previously noted regions of cerebral edema had evolved into multiple encapsulated complex fluid collections predominantly in the bifrontal region suspicious for invasive mucormycosis ( figure 5 and 6 ). neurosurgery was consulted for possible operative intervention. ultimately, the family decided to make the patient comfort care because of her poor prognosis. the patient expired on day 26 of her hospitalization. mucormycosis is rare opportunistic fungal infection characterized by infarction and necrosis of host tissues that results from invasion of the vasculature by hyphae. the most common clinical presentation of mucormycosis is rhino-orbital-cerebral infection, believed to be secondary to inhalation of spores into the paranasal sinuses of a susceptible host [1] . predisposing situations for mucormycosis include diabetes, systemic corticosteroid use, neutropenia, hematologic malignancies, stem cell transplant, and immunocompromised individuals [2] . seventy percent of rhino-orbital-cerebral mucormycosis cases have been found to be in patients with diabetes mellitus, most of whom had also developed ketoacidosis at the time of presentation. infection usually presents with acute sinusitis, fever, nasal congestion, purulent nasal discharge and headache. all the sinuses become involved, and contiguous spread to adjacent structures such as the palate, orbit, and brain results in clinical symptoms. for example, spread of infection from the ethmoid sinus to the frontal lobe results in obtundation. clinical suspicion and early treatment with surgical debridement are key to preventing morbidity in this often-fatal condition. histopathology, direct microscopy, and culture from clinical specimens are the major diagnostic modalities for mucormycosis [3] . the incident rate of mucormycosis varies from 0.005 to 1.7 per million population [4] . the global mucormycosis case fatality rate is 46% [5] . mucormycosis is difficult to diagnosis. early diagnosis and treatment are essential, as a delay of even 6 days is associated with a doubling of 30-day mortality from 35% to 66%. despite early diagnosis and aggressive combined surgical and medical therapy, the prognosis for recovery from mucormycosis is poor. a high suspicion for this disease must be considered in patients who are immunocompromised. in high-risk individuals, this diagnosis should be suspected if there is unilateral facial pain or swelling, orbital swelling, or proptosis. tissue necrosis, often a late sign, is a hallmark of mucormycosis, resulting from angioinvasion and vascular thrombosis. once the diagnosis is considered, empiric antifungal treatment should be started. prompt surgical opinion should also be sought. orbital compartment syndrome (ocs) results from an expansile process within the closed compartment of the orbit leading to increased orbital pressure, and potentially resulting in ischemia and vision loss. it is a true ophthalmologic emergency that requires lateral canthotomy and inferior cantholysis to decompress the orbit. delay in care can lead to permanent blindness. this diagnosis should be suspected in patients presenting with acute proptosis, elevated intraocular pressure, rapid vision loss, ophthalmoplegia, fixed dilated pupil or afferent pupillary defect. causes of ocs can be retrobulbar hemorrhage (from trauma, vascular malformations, tumors), cellulitis or other infection, orbital malignancy, or previous orbital surgery [6] . my review of the literature indicates that this is likely the first documented case of mucormycosis in combination with covid-19 infection. it is impossible to know for certain whether this patient's covid-19 infection was contributory to her illness or merely coincidental. in my opinion, the patient's severe immunocompromised state from untreated diabetes, and ultimately diabetic ketoacidosis is what made her susceptible to contract both mucormycosis and covid-19. as we learn more about covid-19, and continue seeing more patients with this illness, we likely will continue seeing other unique presentations of other disease entities. disease entities in mucormycosis novel perspectives on mucormycosis: pathophysiology, presentation, and management the epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports delaying amphotericin b-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis financial disclosures: none conflicts of interest key: cord-297671-3d3gcn6k authors: venn, april m.r.; schmidt, james m.; mullan, paul c. title: a case series of pediatric croup with covid-19 date: 2020-09-15 journal: am j emerg med doi: 10.1016/j.ajem.2020.09.034 sha: doc_id: 297671 cord_uid: 3d3gcn6k we describe three previously healthy children, admitted from our emergency department (ed) to our free-standing children's hospital, as the first documented cases of croup as a manifestation of sars-cov-2 infection. all three cases (ages 11 months, 2 years, and 9 years old) presented with non-specific upper-respiratory-tract symptoms that developed into a barky cough with associated stridor at rest and respiratory distress. all were diagnosed with sars-cov-2 by polymerase chain reaction testing from nasopharyngeal samples that were negative for all other pathogens including the most common etiologies for croup. each received multiple (≥3) doses of nebulized racemic epinephrine with minimal to no improvement shortly after medication. all had a prolonged period of time from ed presentation until the resolution of their stridor at rest (13, 19, and 21 h). all received dexamethasone early in their ed treatment and all were admitted. all three received at least one additional dose of dexamethasone, an atypical treatment occurrence in our hospital, due to each patient's prolonged duration of symptoms. one child required heliox therapy and admission to intensive care. all patients were eventually discharged. pathogen testing is usually not indicated in croup, but with “covid-19 croup,” sars-cov-2 testing should be considered given the prognostic significance and prolonged quarantine implications. our limited experience with this newly described covid-19 croup condition suggests that cases can present with significant pathology and might not improve as rapidly as those with typical croup. the novel 2019 coronavirus sars-cov-2, responsible for covid-19 disease, commonly presents in children with fever, cough or shortness of breath. [1] [2] [3] other findings can include rhinorrhea, nausea, vomiting, fatigue, diarrhea, dehydration, abdominal pain, headache, pharyngitis, rash, myalgia, cyanosis, tachypnea, tachycardia, apnea, and other presentations. [1, [3] [4] [5] we are unaware of any reports of sars-cov-2 associated with stridor and croup. croup (laryngotracheitis) is usually caused by viral infections (most commonly parainfluenza types 1 to 3) in the fall and winter months. [6] croup typically presents with a "barky cough" and in more severe cases may develop stridor and dyspnea. [7] after an electronic health record database review, we describe this ca 1 se series of our ed's only three cases, between march 1, 2020 and july 31, 2020, of children who received nebulized racemic epinephrine (nre) and had a positive sars-cov-2 infection. in june, an 11-month-old previously healthy african-american male twin, with no sick contacts, presented with one day of cough, fever, and rhinorrhea. on ed arrival, he was febrile (104.9°c), tachypneic (56/minute), and had a 97% oxygen saturation. his exam at rest was notable for biphasic stridor, barky cough, moderate retractions, decreased aeration, and no wheeze. oral dexamethasone (0.6 mg/kg) and nre (0.5ml of 2.25% in saline) were j o u r n a l p r e -p r o o f administered without improvement. a second nre two hours later did not resolve the stridor and he was admitted. a nasopharyngeal respiratory pathogen pcr panel (biofire® filmarray® respiratory rp2.1) was positive for sars-cov2 and negative for all other pathogens. as an inpatient, he got a third nre three hours after the second one, with no response. his stridor continued 21 hours after the initial dexamethasone. as an inpatient, he received a second oral dexamethasone (0.6 mg/kg), 24 hours after the first dose, an infrequent occurrence on the inpatient service for croup. he was discharged after 32 hours of hospitalization. at discharge, he had stridor with exertion only. on phone follow-up, the mother reported that "his breathing got much better the day after he was discharged." in june, a 2-year-old previously healthy caucasian female presented with two days of cough and dyspnea without fever. she had two prior episodes of stridor with upper-respiratory tract infections. the day prior, a telehealth physician diagnosed her with an upper-respiratory tract infection. her father and sister both had fever but had not had sars-cov-2 testing. on ed arrival, she was afebrile (37.0°c), tachycardic (144/minute), tachypneic (44/minute), and had a 99% oxygen saturation. she had stridor at rest with moderate retractions, barky cough, decreased aeration, no wheeze, a normal cardiac exam, and a blanching maculopapular truncal rash. oral dexamethasone (0.6mg/kg) and nre were administered. a second nre was given fifty minutes later for persistent stridor and retractions. two-view neck radiographs revealed mild subglottic narrowing with no radiopaque foreign body. chest radiographs were normal. her nasopharyngeal pcr panel was also positive for an isolated sars-cov2 infection. she was admitted and was treated with a third nre for persistent stridor, 2.5 hours after the previous one, with no response. otorhinolaryngology was consulted for persistent stridor and ultimately recommended dexamethasone (0.6 mg/kg) every 6 hours for 24 hours for severe croup. she had stridor at rest for 13 hours after the first dexamethasone and was discharged 17 hours after admission with stridor only with exertion. on follow-up, the mother reported improved symptoms within one week, but two months later has noted that her daughter "gets winded easily" and is "not back at full capacity." in july, a 9-year-old previously healthy female presented as a transfer from an outside ed with a complaint of coughing. her mother had tested positive for covid-19 ten days before presentation, and the patient's symptoms started three days after her mother's test. her pediatrician advised the family to seek ed care only if she developed respiratory distress. on day six of illness, the coughing became barky without any improvement with dextromethorphanacetaminophen-doxylamine succinate, so she presented to an adult ed. she was febrile (100.5° f), tachypneic (42 breaths/minute) and had a 95% oxygen saturation. for her respiratory distress and inspiratory stridor at rest, she was given racemic epinephrine, codeine, and lorazepam. two hours later, she was speaking in full sentences and breathing at 28 breaths/minute. after a normal chest radiograph, and a nasopharyngeal viral pcr panel that was positive only for sars-cov-2, she was discharged. twelve hours later, she returned to the same ed with "continuous barky coughing," tachypnea (56 breaths/minute), inspiratory stridor at rest, and an oxygen saturation of 94%. a repeat chest radiograph showed "subtle patchy opacities in both lower lobes may represent early j o u r n a l p r e -p r o o f pneumonia" which was treated with ceftriaxone. she received nebulized normal saline and four puffs of an albuterol inhaler with no response. the ed physician consulted us and we recommended nre and dexamethasone. a complete metabolic panel and complete blood count was unremarkable with a c reactive protein of 1.8 milligrams/deciliter. en route by ambulance, she received her third nre with no response. on arrival to our ed, she had a heart rate of 150/minute, respiratory rate of 34/minute, blood pressure of 125/72, and an oxygen saturation of 98%. she was air-hungry, diaphoretic, spoke in a hoarse whisper, separated by back-to-back barky coughs every minute, and complained of chest pain with coughing. her exam revealed severe work of breathing, inspiratory stridor at rest, poor aeration, and no wheeze. her venous blood gas had a ph of 7.43 with a pco2 of 34. a fourth nre made her distress worse. next, bipap was trialed but she could not tolerate it. a two-minute trial of prone positioning also failed. a three-minute trial of heliox (70% helium/30% oxygen) was given with no improvement and was discontinued. the patient was transported to the pediatric intensive care unit (picu) on oxygen by non-rebreather mask with intubation equipment if needed. in the picu, another bipap trial failed and the patient was given iv midazolam (0.05 mg/kg) for anxiolysis. heliox was trialed again as a last attempt before intubation. her respiratory effort slowly improved on heliox which she received for 22 hours along with a dexmedetomidine infusion. her tachypnea resolved after four hours on heliox and her stridor at rest lasted for 19 hours after the initial dexamethasone. she was started on dexamethasone (0.25 mg/kg) iv every 6 hours for 48 hours and switched to oral dosing for 24 hours. remdesivir iv was given for five days. repeat chest radiographs showed no pneumonia and she received no further antibiotics. over four days in the picu, she received intermittent heliox and j o u r n a l p r e -p r o o f benzodiazepines to treat her air hunger and respiratory distress. she was discharged after one additional day on the inpatient service. her mother noted that she was "fully recovered" from all symptoms one week after discharge. this case series describes the first three cases, to our knowledge, of isolated sars-cov-2 infection with pediatric croup. all three were tested with pcr-based pathogen panels that screened for the most common etiologies of croup. [8] in most clinical circumstances, determining the etiology of croup is rarely helpful. [8] in this current pandemic, however, identifying if pediatric croup is associated with sars-cov-2 infection assumes novel importance for counseling inpatient and outpatient families on quarantine and home isolation precautions. [9] given that historical peak incidence of croup is in the upcoming fall and winter months, these cases highlight the importance of inpatient and outpatient access to rapid sars-cov-2 testing. [10] medical advice was sought before ed care in two of these described cases, underscoring the importance of good anticipatory guidance for seeking acute care. their course of acute care was atypical in severity, with potential implications for the expected natural history and management of future cases. there might have been additional cases of covid-19 croup without stridor, who did not require racemic epinephrine, in our ed. these cases were not included in our electronic heathy record query due to our local practice standards of not testing most patients who meet discharge criteria sars-cov-2 infection. given the quarantine implications of discovering sars-cov-2 infection in children, regardless of their clinical severity, our testing practices have changed to now test all croup patients for sars-cov-2. all three of the described covid-19 croup patients had stridor at rest which was j o u r n a l p r e -p r o o f relatively unresponsive to multiple nre treatments. nre reduces croup symptom scores by decreasing upper airway edema, a finding that might be commonly seen with covid-19 pathophysiology. [11] [12] [13] [14] while this case series is limited to only three patients, all had ≥3 total nre treatments, dexamethasone, and additional inpatient interventions (i.e., additional nre, bipap, or heliox). inpatient interventions for croup are relatively infrequent (22.6% in one study), suggesting potentially more severe pathophysiology with covid-19 croup versus previously described croup. [15] pediatric croup patients who received ≥3 nre in one children's hospital were more likely to need intensive care management. [16] the receipt of nre in covid-19 croup patients also introduce concerns given the aerosol-generating nature of the procedure and the required personal protective equipment needs. [17] dexamethasone is used in croup as it improves symptoms, decreases hospital length of stay, and reduces return visit rates. [18] all three cases received multiple doses of dexamethasone, a therapeutic decision that is infrequent for our hospital's practice and is reserved for atypical cases not responding as expected to initial treatments. [19] symptom scores with dexamethasone typically improve in 0.5 to 4 hours. [18, 20] while we did not have longitudinal croup symptom scores (e.g., westley scores), the time from initial dexamethasone to the resolution of stridor at rest ranged from 13 to 21 hours. [21] this is significantly longer than our normal expectations for moderate to severe croup. current covid-19 guidelines recommend dexamethasone for adults who are mechanically ventilated or require oxygen. [22, 23] further study is warranted to determine effective steroid recommendations for pediatric covid-19 croup patients. new covid-19 clinical presentations are emerging rapidly, outpaced "only by the transmission of the virus itself." [24] our limited experience with this newly described covid-19 croup suggests that cases can present with severe pathology and might not improve as rapidly with treatments as in typical croup patients. testing for sars-cov-2 in pediatric croup assumes novel importance during this pandemic for both prognostic and quarantine implications. further investigations are needed to determine the natural history and optimal management of covid-19 croup. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. sars-cov-2 infection in children epidemiology of covid-19 among children in china children with covid-19 in pediatric emergency departments in italy immune thrombocytopenia (itp) in a pediatric patient positive for sars-cov-2 neurologic and radiographic findings associated with covid-19 infection in children racemic epinephrine use in croup and disposition acute management of croup in the emergency department. paediatrics & child health information for pediatric healthcare providers epidemiological analysis of croup in the emergency department using two national datasets nebulized epinephrine for croup in children viral croup: current diagnosis and treatment laryngeal oedema associated with covid-19 complicating airway management pathology and pathogenesis of sars-cov-2 associated with fatal coronavirus disease, united states hospital course of croup after emergency department management rate of airway intervention for croup at a tertiary children's hospital 2015-2016 interim infection prevention and control recommendations for healthcare personnel during the coronavirus disease glucocorticoids for croup in children best practice: one or two doses of dexamethasone for the treatment of croup? archives of disease in childhood how fast does oral dexamethasone work in mild to moderately severe croup? a randomized double-blinded clinical trial: oral dexamethasone for croup nebulized racemic epinephrine by ippb for the treatment of croup: a double-blind study dexamethasone in hospitalized patients with covid-19 -preliminary report centers for disease c, prevention. covid-19 treatment guidelines: corticosteroids covid-19 in children: initial characterization of the pediatric disease key: cord-344136-k5gh0s6y authors: ouyang, lichen; gong, yeli; zhu, yan; gong, jie title: association of acute kidney injury with the severity and mortality of sars-cov-2 infection: a meta-analysis date: 2020-09-02 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.089 sha: doc_id: 344136 cord_uid: k5gh0s6y background: we aimed to explore the relationship of acute kidney injury (aki) with the severity and mortality of coronavirus disease 2019 (covid-19). methods: a systematic literature search was conducted in pubmed, embase, scopus, web of science, medrxiv database. we compared the laboratory indicators of renal impairment and incidences of aki in the severe versus non-severe cases, and survival versus non-survival cases, respectively. results: in 41 studies with 10,335 covid-19 patients, the serum creatinine (scr) in severe cases was much higher than that in non-severe cases (smd = 0.34, 95% ci: 0.29–0.39), with a similar trend for blood urea nitrogen (bun) (smd = 0.66, 95%ci: 0.51–0.81), hematuria (or = 1.59, 95% ci: 1.15–2.19), and proteinuria (or = 2.92, 95% ci: 1.58–5.38). the estimated glomerular filtration rate decreased significantly in severe cases compared with non-severe cases (smd = -0.45, 95% ci: −0.67–0.23). moreover, the pooled or of continuous renal replacement therapy (crrt) and aki prevalence for severe vs. non-severe cases was 12.99 (95%ci: 4.03–41.89) and 13.16 (95%ci: 10.16–17.05), respectively. additionally, 11 studies with 3759 covid-19 patients were included for analysis of disease mortality. the results showed the levels of scr and bun in non-survival cases remarkably elevated compared with survival patients, respectively (smd = 0.97, smd = 1.49). the pooled or of crrt and aki prevalence for non-survival vs. survival cases was 31.51 (95%ci: 6.55–151.59) and 77.48 (95%ci: 24.52–244.85), respectively. conclusions: aki is closely related with severity and mortality of covid-19, which gives awareness for doctors to pay more attention for risk screening, early identification and timely treatment of aki. coronavirus disease 2019 (covid19) , a newly emerging acute respiratory disease, is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and causes substantial morbidity and mortality [1] . as of 12 june 2020, 7519566 covid-19 cases have been confirmed and 419447 people died from covid-19 in more than 200 countries around the world. most patients with covid-19 are considered as non-severe patients and recover from this infection. however, the symptoms in about 10% of covid-19 patients are severe and progress rapidly to critical conditions, including organ dysfunctions, such as acute respiratory distress syndrome (ards), acute cardiac injury, acute kidney injury (aki) and even death [2] . meta-analysis to investigate the association of aki with the severity and mortality of sars-cov-2 infection. the systematic review and meta-analysis were performed according to the recommendations of the cochrane handbook for systematic reviews of interventions and reported based on preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines [6, 7] . this meta-analysis has no protocol. articles published from december 2019 to 8 june 2020 in pubmed, embase, web of science, scopes, and medrxiv database were searched. to identify all the articles displaying the renal impairment in covid-19, we used the following terms alone or in combination for literature search: "sars-cov-2", "covid-19", "2019-ncov", "ncov", "covid19", "coronavirus", "severe acute respiratory rate ≥30 bpm; ii, finger spo 2 ≤93% at rest; iii, ards or arterial partial pressure of oxygen/fraction of inspired oxygen≤300 mmhg; iv, respiratory failure (requiring mechanical ventilation); v, shock; vi, other organ failure (requiring icu monitoring and treatment) [9] . two investigators worked independently to decide which studies should be included, and the disagreement was resolved by a third investigator. data was extracted from selected studies including the first author's name, publication data, sex, average age, numbers of patients and study type. in addition, laboratory examinations of renal impairments including bun, scr, egfr, proteinuria and hematuria, and incidence of aki and crrt were also extracted. the data shown as median and interquartile range was transformed into mean and standard deviation (sd) according to the formula below (http://www.math. hkbu.edu.hk/~tongt/papers/median2mean. html). the prevalence of proteinuria, hematuria, crrt and aki as well as average means of bun, scr and egfr were evaluated between severe and non-severe group or survival and non-survival group, respectively. all data was analyzed by the review manager meta-analysis software (version 5.4). the standardized mean differences (smds) and 95% confidence intervals (cis) were calculated for continuous data. the odds ratios (ors) and 95% cis were calculated for dichotomous data. the magnitude of heterogeneity between different studies was tested using i 2 statistics. if there was no evidence of between studies heterogeneity (i 2 ≤ 50%), a fixed-effects model was used to calculate. otherwise, a random-effects model was selected [10] . the z score was tested for overall effect, with significance considered as p<0.05. publication bias was evaluated by funnel plot if the number of included studies > 10. we searched a total of 2893 articles according to the search terms. firstly, duplicated articles (n=597) were excluded. after reviewing the titles and abstracts, case reports, reviews, letters, meta-analysis, editorials, guidelines, comments, not relevant studies and sample size less than 20 (n=2150) were ruled out. 94 articles were excluded after thoroughly reviewing the full texts due to the following reasons: studies focused on special populations (n=35); studies without available data (n=47), studies with sample less than 20 (n=12). finally, 52 articles[1-4, 9, with 14094 patients were included in our meta-analysis. figure as shown in table 1 , most of studies were from china, and six studies were published from other countries [11,12,25, 15, 19, 22, 24, 25, 35, 40, 48, 52, 53] . the incidence of aki and crrt during sars-cov-2 infections was evaluated between the severe versus non-severe cases or survival versus non-survival cases, respectively. as shown in figure 2a , scr was measured in nine studies among 2345 patients. the heterogeneity test of scr was shown as i 2 =53%, thus we applied the random-effects model for further investigation. the following results elucidated that scr was significantly higher in non-survival group than that in survival group [smd=0.97, group ( figure 2c ). the heterogeneity test of aki was shown as i 2 =0. pooled analysis of four studies among 792 covid-19 patients revealed that the incidence of aki was statistically higher in non-survival group (30.72%) compared with survival group as illustrated in figure 3 as severity of illness was related with complication in covid-19, we also evaluated the incidence of aki in severe and non-severe group ( figure 5a ). the heterogeneity test of aki was shown as i 2 =20%. 19 studies among 4968 covid-19 patients reported that the incidence of aki was shown to be 26.74% in severe group, which was significant higher than that in non-severe group in addition, we also performed meta-analysis on the incidence of hematuria of 664 covid-19 patients with no statistical heterogeneity among 4 studies (i 2 =47%). the incidence of hematuria in severe group was statistically higher compared with non-severe group [or=1.59, 95% ci (1. 15-2.19) , z=2.83, p=0.005] ( figure 5c ). our meta-analysis including 14094 subjects from 52 studies explored the potential relationship between renal impairment as well as aki and the clinical outcome j o u r n a l p r e -p r o o f journal pre-proof (severity and mortality) of covid-19 patients. to our knowledge, this is the first systemic review and meta-analysis which evaluated the kidney function and prevalence of aki between survival and non-survival cases. we found that the prevalence of aki in non-survival cases was 30.72%, which was approximately 77.48-fold higher than that in survival cases. furthermore, patients who died of covid-19 displayed higher baseline of scr and bun as well as higher application rate of crrt than the survival cases. meanwhile, our results including severe and non-severe cases (41 studies, 10335 patients) demonstrated that the overall rate of aki in severe cases was 13.16-fold higher compared with non-severe cases. the levels of scr and bun were shown elevated, while egfr was decreased in severe cases compared with non-severe cases. in addition, the average ratio of proteinuria, hematuria and crrt were 2.92-fold, 1.59-fold and 12.99-fold in severe cases compared with those in non-severe cases, respectively. currently, the exact mechanism of renal impairment involved in covid-19 remains unclear. one potential explanation is direct virus attack mediated via angiotensin-converting enzyme 2 (ace2). rna sequencing studies found that ace2, the novel protein of coronavirus receptor, was highly expressed in proximal renal tubules, which could explain that the urinary analysis was obviously abnormal in covid-19 patients [58] . hence, early detection of urinary analysis is important for preventing the occurrence of aki. in addition, hyper-activated immune response may be partly responsible for the development of kidney damage. clinical studies have shown that the levels of inflammatory cytokines in severe patients are significantly j o u r n a l p r e -p r o o f journal pre-proof increased compared with mild patients [30] . a recent biopsy pathology result of a covid-19 patient with ards demonstrated that the numbers of cd4 + and cd8 + t cells in peripheral blood were greatly reduced, while t cells were excessively activated [59] . these above findings indicated that pathological waterfall-like cytokines storm caused by immune dysregulation may be involved in the occurrence and development of aki and multiple organ dysfunctions. additionally, patients with covid-19, especially severe and critical cases, are prone to complications such as sepsis, shock, and hypovolemia, which could cause the occurrence or aggravation of aki through excessive inflammatory responses, apoptosis, and mitochondrial stress [60] . therefore, optimizing fluid volume and maintaining hemodynamic stability are crucial for severe covid patients to ensure adequate and effective perfusion pressure of the kidney, which could prevent the occurrence or progression of aki. there are strengths of this meta-analysis. to the best of our knowledge, this is the first large meta-analysis which performed a pairwise comparison of kidney function indicators and prevalence of aki in severe vs. non-severe or non-survival vs. survival cases, respectively. secondly, we have included a large number of studies covering six countries, with patient population above fourteen thousand. finally, our meta-analysis analysis of the clinical characteristics, drug treatments and prognoses of 136 patients with coronavirus disease 2019 quantitative methods in the review of epidemiologic literature compassionate remdesivir treatment of severe covid-19 pneumonia in intensive care unit (icu) and non-icu patients: clinical outcome and differences in post-treatment hospitalisation status characterization and clinical course of 1000 patients with covid-19 in new york: retrospective case series characterizing clinical progression of covid-19 clinical infectious diseases : an official publication of the infectious diseases society of america clinical features of patients infected with the 2019 novel coronavirus (covid-19 clinical features and laboratory inspection of novel coronavirus pneumonia (covid-19) in xiangyang clinical and immunologic features in severe and moderate forms of coronavirus disease clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to hubei clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (covid-19) in wuhan, china: a retrospective study correlation between the variables collected at admission and progression to severe cases during hospitalization among covid-19 patients in chongqing influence factors of death risk among covid-19 patients in wuhan, china: a hospital-based case-cohort study. medrxiv 30-day mortality in patients hospitalized with covid-19 during the first wave of the italian epidemic: a prospective cohort study a tool to early predict severe corona virus disease 2019 (covid-19) : a multicenter study using the risk nomogram in wuhan and guangdong, china. clinical infectious diseases : an official publication of the infectious diseases society of america clinical characteristics of coronavirus disease 2019 in china risk factors associated with clinical outcomes in 323 covid-19 hospitalized patients in wuhan, china. clinical infectious diseases : an official publication of the infectious diseases society of america clinical features of patients infected with 2019 novel coronavirus in wuhan prognostic factors for covid-19 pneumonia progression to severe symptom based on the earlier clinical features: a retrospective analysis significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio for predicting clinical outcomes in covid-19. medrxiv clinical features and management of severe covid-19: a retrospective study in wuxi neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage the value of urine biochemical parameters in the prediction of the severity of coronavirus disease 2019. clinical chemistry and laboratory medicine clinical features and progression of acute respiratory distress syndrome in coronavirus disease 2019 covid-19 myocarditis and severity factors： an adult cohort study. medrxiv clinical characteristics of hospitalized covid-19 patients renal involvement and early prognosis in patients with covid-19 pneumonia clinical characteristics and outcomes of 2019 in new york city: prospective cohort study epidemiology, risk factors and clinical course of sars-cov-2 infected patients in a swiss university hospital: an observational retrospective study. medrxiv clinical characteristics of imported and second-generation covid-19 cases outside wuhan, china: a multicenter retrospective study. medrxiv clinical features and treatment of covid-19 patients in northeast chongqing clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china elevated serum igm levels indicate poor outcome in patients with coronavirus disease 2019 pneumonia: a retrospective case-control study. medrxiv risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease pneumonia in wuhan, china. jama internal medicine clinical characteristics of sars-cov-2 pneumonia compared to controls in chinese han population. medrxiv clinical characteristics of coronavirus disease blood glucose is a representative of the clustered indicators of multi-organ injury for predicting mortality of covid-19 in wuhan, china. medrxiv myocardial injury is associated with in-hospital mortality of confirmed or suspected covid-19 in wuhan, china: a single center retrospective cohort study. medrxiv clinical features and short-term outcomes of 221 patients with covid-19 in wuhan potential factors for prediction of disease severity of covid-19 patients. medrxiv clinical characteristics of patients with 2019 coronavirus disease in a non-wuhan area of hubei province, china: a retrospective study urinalysis, but not blood biochemistry, detects the early renal-impairment in patients with covid-19. medrxiv cryo-em structure of the 2019-ncov the prefusion conformation pathological findings of covid-19 associated with acute respiratory distress syndrome. the lancet respiratory medicine acute kidney injury in sepsis wang zh 48 china wuhan case-control 116 65(56) key: cord-300132-lbbibqv3 authors: clifford, christopher t.; pour, trevor r.; freeman, robert; reich, david l.; glicksberg, benjamin s.; levine, matthew a.; klang, eyal title: association between covid-19 diagnosis and presenting chief complaint from new york city triage data date: 2020-11-07 journal: am j emerg med doi: 10.1016/j.ajem.2020.11.006 sha: doc_id: 300132 cord_uid: lbbibqv3 background and aim: new york city (nyc) is an epicenter of the covid-19 pandemic in the united states. proper triage of patients with possible covid-19 via chief complaint is critical but not fully optimized. this study aimed to investigate the association between presentation by chief complaints and covid-19 status. methods: we retrospectively analyzed adult emergency department (ed) patient visits from five different nyc hospital campuses (hospital blinded) from march 1, 2020 to may 13, 2020 of patients who underwent nasopharyngeal covid-19 rt-pcr testing. the positive and negative covid-19 cohorts were then assessed for different chief complaints obtained from structured triage data. sub-analysis was performed for patients older than 65 and within chief complaints with high mortality. results: of 11,992 ed patient visits who received covid-19 testing, 6524/11992 (54.4%) were covid-19 positive. 73.5% of fever, 67.7% of shortness of breath, and 65% of cough had covid-19, but others included 57.5% of weakness/fall/altered mental status, 55.5% of glycemic control, and 51.4% of gastrointestinal symptoms. in patients over 65, 76.7% of diarrhea, 73.7% of fatigue, and 69.3% of weakness had covid-19. 45.5% of dehydration, 40.5% of altered mental status, 27% of fall, and 24.6% of hyperglycemia patients experienced mortality. conclusion: a novel high risk covid-19 patient population was identified from chief complaint data, which is different from current suggested cdc guidelines, and may help triage systems to better isolate covid-19 patients. older patients with covid-19 infection presented with more atypical complaints warranting special consideration. covid-19 was associated with higher mortality in a unique group of complaints also warranting special consideration. methods: we retrospectively analyzed adult emergency department (ed) patient visits from five different nyc hospital campuses (hospital blinded) from march 1, 2020 to may 13, 2020 of patients who underwent nasopharyngeal covid-19 rt-pcr testing. the positive and negative covid-19 cohorts were then assessed for different chief complaints obtained from structured triage data. sub-analysis was performed for patients older than 65 and within chief complaints with high mortality. results: of 11,992 ed patient visits who received covid-19 testing, 6524/11992 (54.4%) were covid-19 positive. 73.5% of fever, 67.7% of shortness of breath, and 65% of cough had covid-19, but others included 57.5% of weakness/fall/altered mental status, 55.5% of glycemic control, and 51.4% of gastrointestinal symptoms. in patients over 65, 76.7% of diarrhea, 73.7% of fatigue, and 69.3% of weakness had covid-19. 45.5% of dehydration, 40.5% of altered mental status, 27% of fall, and 24.6% of hyperglycemia patients experienced mortality. conclusion: a novel high risk covid-19 patient population was identified from chief complaint data, which is different from current suggested cdc guidelines, and may help triage systems to better isolate covid-19 patients. older patients with covid-19 infection presented with more atypical complaints warranting special consideration. covid-19 was associated with higher mortality in a unique group of complaints also warranting special consideration. new york city recorded its first case of covid-19 on march 1, 2020 and quickly became a national epicenter for the disease [1] . as of may 13, 2020, new york state not only had more cases than any other state in the us but also had more cases than any other nation [1] . presentation and symptomatology of covid-19 disease has been researched extensively in the chinese population as shown in the who-china joint report that analyzed 55,924 chinese covid-19 cases [2] . yet, the same level of analysis has not been published for the us population. emergency departments (eds) in the us use a triage system that centers on the emergency severity index (esi) to risk stratify patients, a large component of which relies on the chief j o u r n a l p r e -p r o o f complaint. most eds have been relying on the recommended cdc screening tools to help triage covid-19 patients which is also largely based on the chief complaint. these guidelines highlight the common complaints to be: fever (83-99%), cough (59-82%), fatigue (44-70%), anorexia (40-84%), shortness of breath (31-40%), sputum production (28-33%), and myalgias (11-35%) [3] . however, much of this data was obtained from early infection cases in chinese populations. early evidence from the us shows that chief complaints can vary widely for patients presenting to the ed with covid-19. two large scale studies from the new york metropolitan area showed fever on presentation in only 32.1% and 25.5%, respectively [4] , [5] . knowing the common ed chief complaints for covid-19 patients in the us population has the potential to improve resource utilization and through-put operations while reducing infection risk for patients and staff. this study aimed to investigate the association between different triage chief complaints and covid-19 status by retroactively looking at a large set of covid-19 rt-pcr testing done in the ed. this was an observational multicenter retrospective study conducted at (hospital blinded) in new york city. we retrieved adult ed visits (structured data) of patients who underwent nasopharyngeal swab rt-pcr testing from march 1, 2020 to may 13, 2020. the data were further analyzed as it relates to the patients age, sex, race, comorbidities, and outcomes of admission (intubation and mortality). j o u r n a l p r e -p r o o f the institutional review board (irb) of (hospital blinded) approved the use of patient data for this study and waived the requirement for informed consent. the study was conducted at (hospital blinded) in new york city. data were retrieved from five hospital campuses (hospital blinded). we retrieved data for all patients who presented to the eds and were tested in the ed for covid-19 using nasopharyngeal swab real time polymerase chain reaction (rt-pcr) test. the study time frame was between march 1, 2020 and may 13, 2020. structured patient data was retrieved from our electronic health record system, specifically epic (epic systems corporation, verona, wi), and included demographics, known comorbidities from icd codes, and intubation/mortality outcomes. obesity was defined as body mass index (bmi) over 30 kg/m 2 . smoking was defined as a record of either past or present smoking [6] . all chief complaints are recorded by the triage nurse as structured data from a list of complaints. patients can have more than one recorded chief complaint. the analysis was performed with python (ver. 3.6.5). a p-value of < 0.05 was considered statistically significant. categorical variables were compared using chi square test. continuous with 515 repeat ed visits. 54.4% of the rt-pcr tests were covid-19 positive and 45.6% were covid-19 negative. we present the demographics, comorbidity profile, and outcomes of the covid-19 positive and negative patients who presented to the ed in table 1 . triaging patients with possible covid-19 via chief complaint is not yet fully optimized and mainly relies on the suggested cdc screening guidelines [3] . in this study, we analyzed triage complaints in a large cohort of patients tested for covid-19 in a nyc health system. we have shown that covid-19 patients presented with a spectrum of complaints, with particular variety in the elderly population. fever, shortness of breath, cough, and viral symptoms were very likely to be covid-19 positive which is consistent with prior evidence [4] , [8] , [9] , [10] , [11] . yet, a separate grouping of high risk covid-19 patients presented itself in the data such as: weakness/fall/ams, endocrine, gastrointestinal symptoms, and genitourinary symptoms. the weakness/fall/ams category having a high percentage of covid-19 positive patients is fairly novel. one recent case series described four elderly patients presenting with ams [12] and one early study from china showed confusion in 9% of patients [8] . some anecdotal evidence of us doctors warning the public of elderly patients having symptoms of confusion and ams has been published [13] . whether this change in cognition is a problem from global disease (e.g. hypoxia), change in social situation (e.g. poor nutrition intake), or a potential neuroinvasive property of the virus is yet to be determined. the endocrine grouping (hypoglycemia and hyperglycemia) being associated with covid-19 has some supporting evidence. one early chinese study (jan 2020) showed 52% hyperglycemia and 1% hypoglycemia on admission [8] . hyperglycemia at admission has been shown to be a bad prognostic factor in covid-19 and has been postulated that it is marker for increased inflammatory mediators [14] . one study even showed hyperglycemia on day -1 to be the best predictor of radiographic imaging of sars-cov2 regardless of past medical history of diabetes j o u r n a l p r e -p r o o f journal pre-proof [15] . no definitive link between hypoglycemia and covid-19 has been published and further research is needed. gi symptoms have been debated in past papers. some early chinese papers (jan 2020) showed <5% gi symptoms on presentation for covid infection [8] , [16] while other papers showed ⅓ to ½ gi symptoms on presentation [17] , [18] . our gi complaint category showed 51.4% covid-19 positivity which was higher compared to prior papers. this difference in prevalence needs to be further studied but could be from early data being underpowered as well as early testing being too focused on a respiratory virus and therefore not explicitly assessing gi complaints. the genitourinary category has very little evidence and is fairly novel. dysuria has been shown to be a presenting complaint for covid-19 in case studies but seems to be atypical [19] . having a relatively low patient population that presented with gu symptoms (44/16867) is a potential limitation in our data. less frequent covid-19 positivity was shown in complaints related to central nervous system, chest pain, abdominal pain, orthopedics, and psychiatric/substance abuse. some cns complaints such as large-vessel stroke in the young, have been shown to have association with covid-19 but seems to be a relatively rare complication [20] . chest pain, abdominal pain, orthopedic complaints, and psychiatric/substance abuse have not shown to have a particular relationship with covid-19. journal pre-proof these results described in table 2 have significant real-world implications. since the cdc triage guidelines highlight shortness of breath, cough, and fever as the top symptoms to screen for, many eds have created respiratory pods as their high risk covid-19 areas [3] . it may be worth considering the creation of an intermediate risk pod for patients that present with other moderate-high risk categories that are not respiratory related. the low risk categories could then be separated in their own pod as well to prevent them from catching the virus from other patients. waiting for patients to develop classic covid-19 symptoms such as cough and fever could also possibly delay treatment and increase spread of infection if the patient is sent home, especially to a communal living situation. one important caveat with this recommendation is that our data was collected during a time of high covid-19 prevalence in our community, so these practices may only be extrapolated if similar prevalence is present. chief complaints with a higher percentage of covid-19 positive patients in the older demographic included common complaints such as fever, shortness of breath and viral symptoms, but also included certain unique complaints such as alerted mental status, diarrhea, weakness, fatigue, and hyperglycemia. currently there are no studies on presenting complaints of elderly patients with covid-19. it is important for physicians in the ed to test elderly patients for covid-19 if they present with atypical chief complaints as described above in order to reduce spread of the disease amongst a vulnerable population and increase quality of care. in our cohort, some complaints with high mortality and/or intubation/mechanical ventilation (mv) and high covid-19 positivity were expected such as cardiac arrest and respiratory distress. however, the data also highlighted a group of unique complaints that had high mortality morbidity and mortality based on chief complaint is a difficult topic to study and has limited evidence [21] . however, physicians and triage systems should pay special attention to these high mortality presentations and prioritize their care in order to effectively care for mass amounts of patients that present during a pandemic. there were many complaints not included in the results section since they had small n values (appendix b, table 6 ). it is possible that these complaints are too underpowered to make any significant conclusions from. however, a large data set such as this may be the only way to capture outliers with small n values and could yield ideas for future studies. research on covid-19 is still early and rapidly evolving. many communities around the us have not had enough cases to adequately conduct high powered research. with the us seeing a consistent rise in cases in almost every state, it is clear that the covid-19 pandemic will be a problem for the immediate future [22] . thus, research from the new york area about covid-19 is highly valuable so other affected communities may learn how to better their response efforts. the chief complaint is pivotal for triaging ed patients, especially in the era of covid, and thus should be further optimized. approximately 13.4% of our total visits were complaints of "unspecified" or "other." the chief complaint is put in the computer by the initial triage nurse at the front of the ed. when the chief j o u r n a l p r e -p r o o f complaint is unable to be determined (e.g. non-verbal patient, chief complaint not otherwise found in our systems selections, too many complaints, etc) then the patient is given an "unspecified" or "other" label so that they can continue to move along the process and see a physician. a certain level of unspecified and other categories is therefore inevitable in any triage data. this reflects the real-life scenario of a stressed triage system in a time of a pandemic. there was likely a testing bias for patients that were sick enough to be admitted to the hospital as our health system was initially discouraged by the new york state department of health from testing patient with mild to moderate symptoms. there is also the fact that our covid-19 test likely has a false negative rate, which at this time is largely unknown. lastly, ed visits in the us dropped during the peak of the new york covid-19 outbreak by 42% according to the cdc. this likely skewed our data away from certain complaints towards respiratory chief complaints. therefore, our data may not be able to be extrapolated to communities that are not experiencing similar parameters. a novel high risk covid-19 patient population was identified from chief complaint data which warrants a potential change in triage systems to better isolate covid-19 patients from non-covid-19 patients. older patients with covid-19 infection presented with more atypical complaints which warrants physicians taking special precautions in this population. covid-19 was associated with higher mortality in a unique group of complaints which warrants physicians giving special consideration to these presentations. abbreviations: ams = alerted mental status; gi = gastrointestinal; gu = genitourinary; cns = central nervous system 1 cns is comprised of neurological deficit and cva, stroke-like symptoms, and seizures map?%3aembed=yes&%3atoolbar=no&%3atabs=n. accessed report of the who-china joint mission on coronavirus disease 2019 (covid-19) presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area clinical characteristics of covid-19 in new york city morbid obesity as an independent risk factor for covid-19 mortality in hospitalized patients younger than 50 covid-19 testing, epidemic features, hospital outcomes, and household prevalence epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study clinical characteristics and morbidity associated with coronavirus disease 2019 in a series of patients in metropolitan detroit characterization and clinical course of 1000 patients with coronavirus disease 2019 in new york: retrospective case series initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of hubei altered mental status as a novel initial clinical presentation for covid-19 infection in the elderly seniors with covid-19 show unusual symptoms, doctors say. kaiser health news hyperglycemia and the worse prognosis of covid-19. why a fast blood glucose control should be mandatory admission hyperglycemia and radiological findings of sars-cov2 in patients with and without diabetes clinical features of patients infected with 2019 novel coronavirus in wuhan suggestions for infection prevention and control in digestive endoscopy during current 2019-ncov pneumonia outbreak in wuhan high prevalence of concurrent gastrointestinal manifestations in patients with sars-cov-2: early experience from california novel coronavirus (2019-ncov) in disguise large-vessel stroke as a presenting feature of covid-19 in the young emergency department presenting complaints associated with high mortality and the need for intensive care covid-19 united states cases by county key: cord-349561-4mkiwg9k authors: porta, alessandra della; bornstein, kasha; coye, austin; montrief, tim; long, brit; parris, mehruba anwar title: acute chloroquine and hydroxychloroquine toxicity: a review for emergency clinicians date: 2020-07-19 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.030 sha: doc_id: 349561 cord_uid: 4mkiwg9k background: acute chloroquine and hydroxychloroquine toxicity is characterized by a combination of direct cardiovascular effects and electrolyte derangements with resultant dysrhythmias and is associated with significant morbidity and mortality. objective: this review describes acute chloroquine and hydroxychloroquine toxicity, outlines the complex pathophysiologic derangements, and addresses the emergency department (ed) management of this patient population. discussion: chloroquine and hydroxychloroquine are aminoquinoline derivatives widely used in the treatment of rheumatologic diseases including systemic lupus erythematosus and rheumatoid arthritis as well as for malaria prophylaxis. in early 2020, anecdotal reports and preliminary data suggested utility of hydroxychloroquine in attenuating viral loads and symptoms in patients with sars-cov-2 infection. aminoquinoline drugs pose unique and significant toxicological risks, both during their intended use as well as in unsupervised settings by laypersons. the therapeutic range for chloroquine is narrow. acute severe toxicity is associated with 10–30% mortality owing to a combination of direct cardiovascular effects and electrolyte derangements with resultant dysrhythmias. treatment in the ed is focused on decontamination, stabilization of cardiac dysrhythmias, hemodynamic support, electrolyte correction, and seizure prevention. conclusions: an understanding of the pathophysiology of acute chloroquine and hydroxychloroquine toxicity and available emergency treatments can assist emergency clinicians in reducing the immediate morbidity and mortality associated with this disease. j o u r n a l p r e -p r o o f rheumatologic indications, raising concern for toxicological implications in susceptible patients. following the united states food and drug administration emergency use authorization for chloroquine and hydroxychloroquine in the treatment of sars-cov-2, many additional clinical trials with randomization, blinding, and larger sample sizes were initiated to determine the benefit and risks. the largest of these studies, enrolling over 96,000 patients, initially demonstrated increased in-hospital mortality rates in patients treated with chloroquine or hydroxychloroquine. 35 however, that study has since been retracted due to concerns regarding veracity of the data and analyses conducted and inability to conduct an independent and private peer review. 36 additional studies have demonstrated similar findings of increased mortality or did not find any evidence of prevention of primary endpoints, such as need for mechanical ventilation or death in patients treated with aminoquinolines. [37] [38] [39] as of june 2020, there are over 40 ongoing clinical trials actively assessing the efficacy of chloroquine or hydroxychloroquine, demonstrating continued interest in its role as a therapeutic agent for covid-19. furthermore, additional trials targeting frontline healthcare workers are underway to assess for the possible preventative action of these agents. the use of chloroquine or hydroxychloroquine sulfate in combination with other novel antiviral agents has been discouraged by the united states food and drug administration, as recent in-vitro data demonstrating increasing concentrations of chloroquine phosphate reduced formation of activated remdesivir triphosphate in human bronchial epithelial cells, raising concerns that it may reduce the antiviral activity of this medication. 40 widespread non-prescription use of aminoquinolines for either prophylaxis or treatment by laypersons in response to fears of covid-19 raises significant and continued concern for unintended toxicity from overdose and/or drug-drug interactions. despite slight differences in chemical structure, chloroquine and hydroxychloroquine are similar in regard to both metabolism and toxicity. 41, 42 both molecules are highly lipophilic, have a high volume of distribution, and have mild-to-moderate protein binding. 43, 44 following ingestion, the drugs are rapidly absorbed from the upper gastrointestinal (gi) tract and slowly redistribute to other compartments, eventually accumulating in erythrocytes, liver, lung, kidney, heart, muscle, and retinal tissue. 43 the combination of rapid absorption, high oral bioavailability, and slow redistribution prompts early peak serum levels post-ingestion which correlate with symptom severity in overdose. 41 recent trials for covid-19 have used regimens starting with 1 g on day one followed by 500 mg once daily for 4-7 days. 6 median lethal doses (ld50) for chloroquine and hydroxychloroquine in humans are unknown as most available mortality data derives from case reports and case series. as little as 2-3 g of chloroquine may be fatal in adult patients, though the most commonly reported lethal dose in adults is 3-4 g. 19 the minimum lethal dose of chloroquine is estimated at 30-50 mg/kg. 45 whole blood concentrations of 2.5 µg/l and above are considered to be lethal. 46 significant toxicity from hydroxychloroquine has been reported in patients with plasma levels ranging between 2.05-18. 16 enzymes. 47 intrinsic liver disease, such as hepatitis, alcoholism, or those taking additional medications metabolized by the same p450 isozymes can also modify chloroquine and hydroxychloroquine metabolism. 48 following hepatic metabolism, aminoquinolines are mainly excreted renally (table 1) . a small percentage of the initial ingested quantity of chloroquine or hydroxychloroquine is excreted unchanged. 49 plasma half-life is extended in patients with renal insufficiency. 50 chloroquine and hydroxychloroquine are distinct in terms of serum concentration required to produce toxicity, as chloroquine produces lethal effects at approximately 25% of the serum concentration of hydroxychloroquine. 45 however, both drugs have similar mechanisms of action. aminoquinolines are pharmacologically diverse with activity on many distinct organ systems, cellular receptor sites, and intracellular organelles. this versatility contributes to the myriad uses of aminoquinolines from antimalarial prophylaxis to immunomodulation. 51 most acutely lethal in cases of toxicity is the ability of aminoquinolines to inhibit myocardial sodium and potassium channels. 52 they behave as class ia antiarrhythmics with "quinidine-like" effects, decreasing inotropy and producing characteristic electrocardiographic (ecg) changes. 52 aminoquinolines also cause α 1 -adrenergic receptor blockade with loss of vascular sympathetic tone and resultant j o u r n a l p r e -p r o o f hypotension. 52 finally, aminoquinolines have the ability to bind to and inhibit atp-dependent potassium channels on pancreatic β-cells leading to a similar mechanism of systemic release of insulin as is observed with sulfonylureas. 53 acute aminoquinoline toxicity affects multiple organ systems. the following sections describe effects from acute and chronic toxicity. many of the features of aminoquinoline toxicity are pertinent to ed care, particularly serum abnormalities and cardiac, respiratory, and neurologic phenomena. others may occur following admission or discharge from the ed and become more relevant in the context of patient history, including otologic and ophthalmic sequelae. a summary of these findings is displayed in table 2 . patient outcomes in acute toxicity depend on the degree of observed cardiovascular dysfunction. 20, 54 aminoquinolines produce multiple effects on cardiac electrical conduction via sodium and potassium channel inhibition and α 1 -adrenergic receptor antagonism as previously mentioned. 20 similar to class i antiarrhythmics, aminoquinolines have a dose-dependent effect on the cardiac action potential; the drug binds more avidly to ion channels and exerts greater sodium channel blockade at faster heart rates. 52 the effect leads to the classic pr prolongation, qrs complex widening, and qt prolongation associated with toxicity. 55 also similar to class ia antiarrhythmics is the dose-dependent ability of aminoquinolines to bind and inhibit the action of potassium channels. as potassium is responsible for myocyte repolarization, potassium channel blockade delays repolarization. clinically, this produces additional qt prolongation and j o u r n a l p r e -p r o o f predisposes to torsades de pointes (tdp). 52 delay of repolarization is greatest at slower heart rates. 52 acute cardiac toxicity manifests as conduction blocks involving the atrioventricular junction and his-purkinje system and ecg changes with prolongation in pr, qrs, and qt intervals. 11, 52 following overdose, these abnormalities can be profound, with reports of corrected qt (qtc) intervals of 563 milliseconds (ms) and 600 ms in case reports detailing oral hydroxychloroquine overdoses of 36 g and 22 g, respectively. 42 dysrhythmias are typically present in moderate to severe toxicity. 52, 56 patients with underlying prolonged qtc from structural heart disease, congenital long-qt syndromes, electrolyte disturbances, renal failure, and/or use of additional qt prolonging medications are at heightened risk for development of dysrhythmias including tdp. 56, 57 hydroxychloroquine induced conduction delay often presents as a progression from a singular fascicular block to bundle branch block, followed by third-degree av block. 58 secondary to α 1 -adrenergic blockade, acutely toxic patients present with hypotension, which in addition to dysrhythmias may cause presyncope or syncope. 59 while unlikely to occur in acute overdose, cardiomyopathy is described in case reports of patients presenting with chronic chloroquine and/or hydroxychloroquine toxicity. 60, 61 aminoquinoline-induced cardiomyopathy is believed to result from lysosomal dysfunction and toxic phospholipid accumulation in cardiomyocytes. 61 aminoquinoline-related cardiomyopathy has been reported with findings of biatrial and/or biventricular enlargement as well as concentric hypertrophy with restrictive features. 62 chronic exposure to cumulative doses of 1277 g and 1843 g of chloroquine and hydroxychloroquine, respectively, over an average of 13 years has j o u r n a l p r e -p r o o f been demonstrated to produce this effect. 63 risk of development is greater in patients with underlying heart failure or structural heart defects. sequelae of drug-induced cardiomyopathy include acute and chronic heart failure, recurrent syncopal episodes, and newly developed conduction disorders. 52, 55 serum abnormalities plasma potassium levels vary inversely with the degree of blood chloroquine concentrations. 11, 64, 65 hypokalemia is invariably present in overdose, and the extent of hypokalemia is an indicator of the severity of overdose. 54, 64 treatment-refractory hypokalemia is often one of the most challenging features following acute intoxication and is associated with cardiac manifestations including dysrhythmias. 64, 66 case reports from acute overdose report serum potassium concentrations of 2.5-2.7 meq/l despite management with up to 280 meq of potassium chloride. 66 the mechanism underlying hypokalemia is believed to be due to an intracellular shift of potassium as opposed to total body depletion, as aminoquinolines cause blockade of potassium channels on the pancreatic β-cells. 42, 64, 67 similar to the mechanism of action of sulfonylureas, hyperinsulinism can produce additional serum abnormalities of hypoglycemia, particularly in patients with underlying metabolic derangements. 68, 69 j o u r n a l p r e -p r o o f ophthalmologic sequelae of acute aminoquinoline intoxication include diplopia, loss of visual acuity, tunnel vision, mydriasis, and scotomata. 81 onset of ocular symptoms often follows other clinical presentations, such as arrhythmia or hypotension by several hours. vision improvement may occur rapidly or have a protracted recovery course of months following exposure. 81 retinal toxicity has been reported at higher cumulative aminoquinoline doses, most often seen with chronic use. following cumulative doses of 1000 g, the prevalence of retinal toxicity increases to 1% and is associated with an irreversible loss of vision despite cessation of the drug. 82 in some cases, progression of vision loss is present for up to one year after discontinuation of the offending agent. vision loss is often bilateral and is characterized as a "bull's-eye" maculopathy and depigmentation of the retinal pigment epithelium (rpe). 83 this begins in the central visual fields, but with continued exposure leads to atrophy of the rpe and visual acuity loss. the mechanism underlying toxicity to the cells of the retina is believed to be multifactorial, including direct photoreceptors damage via alterations in metabolism and secondary effects due to the binding of aminoquinolines to the melanin cells within the rpe. 83 as opposed to quinine, aminoquinoline toxicity is less commonly associated with acute onset of gi symptoms such as nausea, vomiting, and diarrhea. while these may occur in both acute toxicity and in chronic therapeutic use, there are no long-term gi sequelae. 51 aminoquinolinerelated nausea and vomiting is mediated both by direct gastric irritant effects and activation of emetic centers in the brain. 84 symptoms are usually transient following acute intoxication or therapeutic doses. 84 fewer than 1% of patients display an increase in transaminases following j o u r n a l p r e -p r o o f initiation of aminoquinolines. 85 case reports of drug induced liver injury (dili) have reported ast and alt elevations of 399 iu/l and 285 iu/l, respectively, within eight hours of initial dosing. 86, 87 however, in patients with underlying liver disease or porphyria cutanea tarda, dili has been reported in up to 50% of cases, and observed transaminitis may be much more severe. 86, 87 in the majority of cases transaminases returned to baseline following drug discontinuation. 85, 86 myotoxicity similar to the mechanism underlying aminoquinoline-induced cardiomyopathy, lysosomal dysfunction with vacuolar accumulation of metabolic products is believed to play a role in skeletal muscle toxicity. 21 clinically, myopathy tends to be mild when symptomatic and affects the proximal muscles to a greater degree than distal groups, presenting as weakness. 88 while the incidence of chronic aminoquinoline use-induced myopathy is reportedly as high as 12.6%, it is believed to be higher due to two factors. 86, 87 first, patient underreporting is likely, as elevations in creatine phosphokinase may be seen in patients even with normal strength testing. second, myopathy may be difficult to distinguish from baseline, as myopathy-related pain and weakness are often associated with the rheumatologic diseases that these drugs are often prescribed to treat. 88 it is unknown if myopathy is dose-dependent, although myotoxicity progression has been observed with prolonged treatment ( table 2) . 89 j o u r n a l p r e -p r o o f including jaundice, hemoglobinuria, and renal failure. 90, 91 in patients with glucose-6-phosphate dehydrogenase (g6pd) deficiency, hemolysis can occur due to free radical accumulation in erythrocytes. 91, 92 due to a lack of reduced glutathione, oxidative stress denatures heme, causing extravascular hemolysis. the extent of hemolysis depends on the drug, dose, and the degree of enzyme deficiency, leading to a range of asymptomatic to life-threatening hemolysis. 93 primaquine is more closely associated with g6pd-mediated hemolysis. although case report literature describes the finding in chloroquine and hydroxychloroquine use, the largest chart review to date examining these drugs in patients with g6pd noted no occurrence of hemolysis. 91, 92 gold-standard evidence such as randomized controlled trials, systematic reviews, or metanalyses for management of aminoquinoline toxicity do not currently exist in the literature. the following recommendations are based on published expert opinion from poison control centers and medical toxicologists, as well as frequent findings described in case report literature. consultation with a poison control center and/or medical toxicologist is recommended early in the management of these patients in the emergency department. aminoquinoline overdose produces toxicity ranging from mild to severe. unlike with chloroquine overdoses, there is no established lethal or toxic dose of hydroxychloroquine in adults, and management should be tailored to observed toxicity. 22 mild chloroquine toxicity in adults is defined as symptomatology occurring with suspected ingested dose <2 g, normal systolic blood pressure, and normal qrs (≤120 ms). 19 moderate chloroquine toxicity occurs with suspected ingested dose 2-4 g, normal systolic blood pressure, and normal qrs (≤120 ms). 19 severe chloroquine toxicity occurs with suspected ingested dose >4 g, hypotension, and qrs prolongation (>120 ms). 54 doses exceeding 5 g are highly associated with mortality due to arrhythmias and hypokalemia. 94 treatment in the ed setting is focused on high-quality symptomatic and supportive measures, decontamination, stabilization of cardiac dysrhythmias if present, hemodynamic support, and electrolyte correction as necessary. 22 indications for intensive care unit admission include persistent systemic hypotension, qrs elongation >120 ms, ventricular arrhythmias, seizures, coma, and persistent hypoglycemia. 95 multiple reports cite early intubation and mechanical ventilation as critical for survival. the combination of altered mentation, apnea, and vomiting present in many aminoquinoline-intoxicated patients heightens the necessity for early and aggressive airway intervention to reduce aspiration risk. given concerns for rapid potassium shifts in toxicity and repletion, an alternative to succinylcholine should be considered for rapid sequence induction and paralysis to avoid provoking rapid onset of hyperkalemia. additionally, clinicians should avoid barbiturates for induction, as they may precipitate sudden cardiac arrest. 96 in the following sections, strategies for the emergency management of aminoquinoline intoxication will be addressed, including decontamination, pharmacotherapeutics, elimination j o u r n a l p r e -p r o o f methods, and emerging modalities (i.e. ecmo and ile). algorithmic application of these strategies to the categorization of mild, moderate, and severe toxicity is shown in figure 1 . overdose. hydroxychloroquine and chloroquine have high volumes of distribution and significant protein binding, complicating modalities for augmenting elimination. 11 although these drugs are ingested, patients should not receive emetics such as syrup of ipecac, as toxicity sequelae of seizures, altered mentation, dysrhythmias, and hypotension heighten risks of aspiration. 11 similarly, orogastric lavage has fallen out of favor due to the risks of aspiration. in cases of life threatening ingestion, orogastric lavage can be considered in patients presenting early following ingestion, within one hour. 41, 66 activated charcoal effectively absorbs aminoquinoline in the gastrointestinal tract with 95%-99% binding when administered in the first five minutes following ingestion. 97 as with other decontamination strategies, the use of activated charcoal will depend on patient presentation (i.e. those who are not nauseated or vomiting) and duration of intoxication. 11 while serum drug levels may be drawn, they are not readily available and therefore are not a practical measure to guide initial management of acute toxicity in the ed setting. 74 however, for inpatient treatment, early and serial measurements of blood chloroquine concentrations are more accurate compared to estimated oral ingestion for predicting cardiovascular severity of chloroquine poisonings. 98 hypokalemia is a marker of severity of toxicity in acute poisoning and must be carefully monitored and managed as intracellular shifts can reverse as acute toxicity resolves, with rapid onset of hyperkalemia. 11 potassium may be repleted cautiously in severe hypokalemia (<1.9 meq/l), and monitoring of potassium levels should occur regularly. while older studies indicate that hypokalemia may prolong survival, contemporary data favor potassium repletion, generally to >4 meq/l. 64 dysrhythmias resulting from electrolyte derangements including potassium should be rapidly but carefully corrected. 11 class ia, ic, and iii antiarrhythmics should be avoided as they may worsen conduction delays. 11 magnesium sulfate 2g iv over 10 minutes may be used for tdp treatment, but has an unclear role in prophylaxis for qt prolongation ≥500 ms. 100 potassium repletion to achieve serum concentration between 4.7-5. to mechanical ventilation increased survival from 9% to 91%. 20 if epinephrine fails to adequately raise mean arterial pressure, a second pressor such as norepinephrine or phenylephrine can be titrated to effect, though alpha agonists increase the effective refractory period and may increase the occurrence of arrythmias. 103, 104 if hypotension is due to myocardial depression rather than arterial vasodilation, these vasoactive medications may worsen cardiac output. 104 patients requiring additional vasopressor support beyond epinephrine and diazepam should receive close attention to hemodynamic parameters to ensure treatment efficacy. diazepam is used in the management of both hypotension and dysrhythmias in dosages of 2 mg/kg iv over 30 minutes, followed by 1 to 2 mg/kg/d for 2-4 days in severe cases. 51 the mechanism of diazepam in attenuation cardiotoxicity is believed to have a central antagonistic effect, anticonvulsant effect, antidysrhythmic effect and interaction inverse to aminoquinolines, and decrease aminoquinoline induced-vasodilation. 22, 105, 106 experimental use of diazepam in animal models of severe chloroquine overdose demonstrates improved systolic and diastolic arterial pressures, heart rate, urine volume, urinary excretion of chloroquine, and shortened qrs duration. 102, 107 no studies have compared efficacy between different benzodiazepines for treatment of acute aminoquinoline toxicity. with medication shortages or variation in ed pharmacy stock, another benzodiazepine may be substituted for treatment of seizures and for maintenance of sedation. gastrointestinal symptoms, such as nausea, vomiting, and diarrhea, can be found in mildly intoxicated patients and more severe overdoses. vomiting in early stages of intoxication may be due to direct irritant effects of aminoquinolines, and may be better managed with the decontamination strategies addressed above. nausea and vomiting can be treated symptomatically while avoiding qtc prolonging agents such as serotonin antagonists (ondansetron) and phenothiazines (promethazine, prochlorperazine). 108 antihistamine (meclizine) and dopamine receptor antagonist (metoclopramide) antiemetics may be safer options. there are currently no accepted treatments for quinine-induced ocular toxicity, but fundoscopic examination, visual field examination, and color testing are appropriate to assess injury ideally by an ophthalmologist. 19 hyperbaric oxygen has been used successfully in vision recovery, but causality was not established. 109 to address sodium channel, blockade sodium loading with sodium bicarbonate (nahco 3 ), sodium acetate, or hypertonic saline (3% nacl) may be used. 11 consideration should be given to the degree of cardiac toxicity and severity of hypokalemia if present, favoring use of sodium acetate or hypertonic saline to avoid worsening hypokalemia. the ph can be used as an indirect indicator of sodium load. when using nahco 3 , a bolus of 1-2 meq/kg is recommended, repeated as needed to terminate dysrhythmias or narrow qrs complex, then utilizing a nahco 3 infusion. 11 when using sodium acetate, 1 meq/kg body weight may be infused over 15-20 min as a bolus. 110 potassium should be closely monitored for intracellular shifting of potassium with j o u r n a l p r e -p r o o f development of clinically significant hypokalemia. hypertonic saline contains the same quantity of sodium in 97 meq as sodium bicarbonate in 50 meq. when using 3% nacl, a bolus of 2-4 meq/kg may be considered, and sodium levels should be closely monitored. 111 approximately 50% of chloroquine is excreted renally, and acute renal failure is possible following acute intoxication. 112 providers should anticipate the possibility of extended toxicity course in patients with acute and/or chronic renal failure. unfortunately, hemodialysis use has been reported as ineffective due to high protein binding and large volume of distribution intrinsic to the aminoquinolines. 112 case report evidence suggests hemodialysis efficacy can be augmented by use of ile. 22 there are multiple reports of veno-arterial ecmo to successfully treat aminoquinoline toxicity. 98, [113] [114] [115] [116] ecmo may be considered in severe toxicity refractory to standard supportive care and other therapies (i.e. escalation of epinephrine drip rate to > 3 mg/hr, persistent endorgan failure). one case report describes ecmo initiation on intensive care unit admission following a 9.5 g chloroquine ingestion (initial blood chloroquine concentration 6215 µg/l). the patient presented with altered mental status, left ventricular systolic dysfunction with a dyskinetic interventricular septum, and hypotension unresponsive to crystalloid fluid resuscitation as well as 3 mg/hour epinephrine infusion. the patient was weaned from vasopressors on day three, decannulated from ecmo on day four, extubated on day seven, and discharged on day ten with no neurological sequelae. 117 another case detailing ecmo use in a patient experiencing ventricular fibrillation following 12 g hydroxychloroquine overdose noted j o u r n a l p r e -p r o o f "spectacular improvement of hemodynamic parameters and electrocardiographic normalization at day one." 114 owing to the lipophilicity of aminoquinolines, there are several reports of successful outcomes following ile use. 22, 46, 118, 119 recommended ile treatment is 1.5 ml/kg lean body mass (~100ml in adults) as bolus over two to three minutes followed by 200 ml over 10-15 minutes. 22 if benefit is seen in vital signs and/or ecg parameter normalization, slower continuous infusion of ~0.25 ml/kg/min can be administered until resolution of toxicity. 119 combined ile, nahco 3 , and vasopressor support has been reported in profound hydroxychloroquine overdose of 40 g presenting with hypokalemia and refractory ventricular fibrillation with positive outcome. 22 protracted ile has been associated with dysfunction of ecmo circuits, though this is unlikely in short-term ile use (<24 hours continuous infusion), and case reports have described safe concomitant use of both modalities. 118 ,120 serum triglyceride levels may be monitored to guide ile extent of infusion, with ~1000 mg/dl as a lipid volume limit of efficacy. 121 given the wide publicity in the lay media regarding the use of aminoquinolines for covid-19 and trends in national poison control center data, a more current exploration of the acute management of aminoquinoline toxicity is necessary. this class of drugs has a narrow therapeutic range and a large variance in toxic dose from person to person. severe symptoms can occur with doses as small as 1.5 g with onset one to three hours post-ingestion. management of acute toxicity often occurs in the emergency department and should focus on hemodynamic j o u r n a l p r e -p r o o f stabilization with the use of early mechanical ventilation, diazepam, epinephrine, frequent ecgs, and repeated blood glucose monitoring, with early step-up to aggressive resuscitative measures including ecmo to support vital functions until the offending agent is metabolized and cleared. 25, 26 coronavirus disease 2019 (covid-19) , caused by sars-cov-2, is responsible for a major international pandemic with significant morbidity and mortality rates between 1.5-9% depending on the population investigated. 27, 28 the pathophysiology of sars-cov-2 includes but is not limited to cytokine dysregulation, direct cytopathic effects on respiratory tract epitheliocytes, and down-regulation of lung protective angiotensin converting enzyme resulting in diffuse alveolar damage and hypercoagulability. 29, 30 viral entry is facilitated by cellular protease-primed spike protein binding to angiotensin-converting enzyme 2 (ace2) receptors. 31 efforts to repurpose or develop targeted therapeutics for sars-cov-2 infection have included assessment of antiinflammatory drugs such as corticosteroids and interleukin inhibitors, macrolide antibiotics such as azithromycin, and direct-acting antivirals such as protease inhibitors and adenosine analogs. 6 the utility of aminoquinolines in attenuating infection severity is hypothesized to derive from preventing sars-cov-2 binding to target receptors and inhibiting viral cell entry. 6 chloroquine and hydroxychloroquine are concentrated within the endosome, where they are thought to modulate organelle ph, inhibiting autophagosome formation and impairing cleavage of the sars-cov-2 spike protein. 32 additional hypothesized immunomodulatory effects in sarsthat play a role in organ injury and acute respiratory distress syndrome. 32 concern for unintended toxicity from overdose and/or drug-drug interactions. despite slight differences in chemical structure, chloroquine and hydroxychloroquine are similar in regard to both metabolism and toxicity. 41, 42 both molecules are highly lipophilic, have a high volume of distribution, and have mild-to-moderate protein binding. 43, 44 following ingestion, the drugs are rapidly absorbed from the upper gastrointestinal (gi) tract and slowly redistribute to other compartments, eventually accumulating in erythrocytes, liver, lung, kidney, heart, muscle, and retinal tissue. 43 the combination of rapid absorption, high oral bioavailability, and slow redistribution prompts early peak serum levels post-ingestion which correlate with symptom severity in overdose. 41 recent trials for covid-19 have used regimens starting with 1 g on day one followed by 500 mg once daily for 4-7 days. 6 median lethal doses (ld50) for chloroquine and hydroxychloroquine in humans are unknown as most available mortality data derives from case reports and case series. as little as 2-3 g of chloroquine may be fatal in adult patients, though the most commonly reported lethal dose in adults is 3-4 g. 19 the minimum lethal dose of chloroquine is estimated at 30-50 mg/kg. 45 whole blood concentrations of 2.5 µg/l and above are considered to be lethal. 46 enzymes. 47 intrinsic liver disease, such as hepatitis, alcoholism, or those taking additional medications metabolized by the same p450 isozymes can also modify chloroquine and hydroxychloroquine metabolism. 48 following hepatic metabolism, aminoquinolines are mainly excreted renally (table 1) . a small percentage of the initial ingested quantity of chloroquine or hydroxychloroquine is excreted unchanged. 49 plasma half-life is extended in patients with renal insufficiency. 50 chloroquine and hydroxychloroquine are distinct in terms of serum concentration required to produce toxicity, as chloroquine produces lethal effects at approximately 25% of the serum concentration of hydroxychloroquine. 45 however, both drugs have similar mechanisms of action. aminoquinolines are pharmacologically diverse with activity on many distinct organ systems, cellular receptor sites, and intracellular organelles. this versatility contributes to the myriad uses of aminoquinolines from antimalarial prophylaxis to immunomodulation. 51 most acutely lethal in cases of toxicity is the ability of aminoquinolines to inhibit myocardial sodium and potassium channels. 52 they behave as class ia antiarrhythmics with "quinidine-like" effects, decreasing inotropy and producing characteristic electrocardiographic (ecg) changes. 52 aminoquinolines also cause α 1 -adrenergic receptor blockade with loss of vascular sympathetic tone and resultant j o u r n a l p r e -p r o o f hypotension. 52 finally, aminoquinolines have the ability to bind to and inhibit atp-dependent potassium channels on pancreatic β-cells leading to a similar mechanism of systemic release of insulin as is observed with sulfonylureas. 53 acute aminoquinoline toxicity affects multiple organ systems. the following sections describe effects from acute and chronic toxicity. many of the features of aminoquinoline toxicity are pertinent to ed care, particularly serum abnormalities and cardiac, respiratory, and neurologic phenomena. others may occur following admission or discharge from the ed and become more relevant in the context of patient history, including otologic and ophthalmic sequelae. a summary of these findings is displayed in table 2 . patient outcomes in acute toxicity depend on the degree of observed cardiovascular dysfunction. 20,54 aminoquinolines produce multiple effects on cardiac electrical conduction via sodium and potassium channel inhibition and α 1 -adrenergic receptor antagonism as previously mentioned. 20 similar to class i antiarrhythmics, aminoquinolines have a dose-dependent effect on the cardiac action potential; the drug binds more avidly to ion channels and exerts greater sodium channel blockade at faster heart rates. 52 the effect leads to the classic pr prolongation, qrs complex widening, and qt prolongation associated with toxicity. 55 also similar to class ia antiarrhythmics is the dose-dependent ability of aminoquinolines to bind and inhibit the action of potassium channels. as potassium is responsible for myocyte repolarization, potassium channel blockade delays repolarization. clinically, this produces additional qt prolongation and j o u r n a l p r e -p r o o f predisposes to torsades de pointes (tdp). 52 delay of repolarization is greatest at slower heart rates. 52 acute cardiac toxicity manifests as conduction blocks involving the atrioventricular junction and his-purkinje system and ecg changes with prolongation in pr, qrs, and qt intervals. 11, 52 following overdose, these abnormalities can be profound, with reports of corrected qt (qtc) intervals of 563 milliseconds (ms) and 600 ms in case reports detailing oral hydroxychloroquine overdoses of 36 g and 22 g, respectively. 42 dysrhythmias are typically present in moderate to severe toxicity. 52, 56 patients with underlying prolonged qtc from structural heart disease, congenital long-qt syndromes, electrolyte disturbances, renal failure, and/or use of additional qt prolonging medications are at heightened risk for development of dysrhythmias including tdp. 56, 57 hydroxychloroquine induced conduction delay often presents as a progression from a singular fascicular block to bundle branch block, followed by third-degree av block. 58 secondary to α 1 -adrenergic blockade, acutely toxic patients present with hypotension, which in addition to dysrhythmias may cause presyncope or syncope. 59 while unlikely to occur in acute overdose, cardiomyopathy is described in case reports of patients presenting with chronic chloroquine and/or hydroxychloroquine toxicity. 60, 61 aminoquinoline-induced cardiomyopathy is believed to result from lysosomal dysfunction and toxic phospholipid accumulation in cardiomyocytes. 61 aminoquinoline-related cardiomyopathy has been reported with findings of biatrial and/or biventricular enlargement as well as concentric hypertrophy with restrictive features. 62 chronic exposure to cumulative doses of 1277 g and 1843 g of chloroquine and hydroxychloroquine, respectively, over an average of 13 years has j o u r n a l p r e -p r o o f been demonstrated to produce this effect. 63 risk of development is greater in patients with underlying heart failure or structural heart defects. sequelae of drug-induced cardiomyopathy include acute and chronic heart failure, recurrent syncopal episodes, and newly developed conduction disorders. 52, 55 serum abnormalities plasma potassium levels vary inversely with the degree of blood chloroquine concentrations. 11, 64, 65 hypokalemia is invariably present in overdose, and the extent of hypokalemia is an indicator of the severity of overdose. 54, 64 treatment-refractory hypokalemia is often one of the most challenging features following acute intoxication and is associated with cardiac manifestations including dysrhythmias. 64, 66 case reports from acute overdose report serum potassium concentrations of 2.5-2.7 meq/l despite management with up to 280 meq of potassium chloride. 66 the mechanism underlying hypokalemia is believed to be due to an intracellular shift of potassium as opposed to total body depletion, as aminoquinolines cause blockade of potassium channels on the pancreatic β-cells. 42, 64, 67 similar to the mechanism of action of sulfonylureas, hyperinsulinism can produce additional serum abnormalities of hypoglycemia, particularly in patients with underlying metabolic derangements. 68, 69 j o u r n a l p r e -p r o o f ophthalmologic sequelae of acute aminoquinoline intoxication include diplopia, loss of visual acuity, tunnel vision, mydriasis, and scotomata. 81 onset of ocular symptoms often follows other clinical presentations, such as arrhythmia or hypotension by several hours. vision improvement may occur rapidly or have a protracted recovery course of months following exposure. 81 retinal toxicity has been reported at higher cumulative aminoquinoline doses, most often seen with chronic use. following cumulative doses of 1000 g, the prevalence of retinal toxicity increases to 1% and is associated with an irreversible loss of vision despite cessation of the drug. 82 in some cases, progression of vision loss is present for up to one year after discontinuation of the offending agent. vision loss is often bilateral and is characterized as a "bull's-eye" maculopathy and depigmentation of the retinal pigment epithelium (rpe). 83 this begins in the central visual fields, but with continued exposure leads to atrophy of the rpe and visual acuity loss. the mechanism underlying toxicity to the cells of the retina is believed to be multifactorial, including direct photoreceptors damage via alterations in metabolism and secondary effects due to the binding of aminoquinolines to the melanin cells within the rpe. 83 as opposed to quinine, aminoquinoline toxicity is less commonly associated with acute onset of gi symptoms such as nausea, vomiting, and diarrhea. while these may occur in both acute toxicity and in chronic therapeutic use, there are no long-term gi sequelae. 51 aminoquinolinerelated nausea and vomiting is mediated both by direct gastric irritant effects and activation of emetic centers in the brain. 84 symptoms are usually transient following acute intoxication or therapeutic doses. 84 fewer than 1% of patients display an increase in transaminases following j o u r n a l p r e -p r o o f initiation of aminoquinolines. 85 case reports of drug induced liver injury (dili) have reported ast and alt elevations of 399 iu/l and 285 iu/l, respectively, within eight hours of initial dosing. 86, 87 however, in patients with underlying liver disease or porphyria cutanea tarda, dili has been reported in up to 50% of cases, and observed transaminitis may be much more severe. 86, 87 in the majority of cases transaminases returned to baseline following drug discontinuation. 85, 86 myotoxicity similar to the mechanism underlying aminoquinoline-induced cardiomyopathy, lysosomal dysfunction with vacuolar accumulation of metabolic products is believed to play a role in skeletal muscle toxicity. 21 clinically, myopathy tends to be mild when symptomatic and affects the proximal muscles to a greater degree than distal groups, presenting as weakness. 88 while the incidence of chronic aminoquinoline use-induced myopathy is reportedly as high as 12.6%, it is believed to be higher due to two factors. 86, 87 first, patient underreporting is likely, as elevations in creatine phosphokinase may be seen in patients even with normal strength testing. second, myopathy may be difficult to distinguish from baseline, as myopathy-related pain and weakness are often associated with the rheumatologic diseases that these drugs are often prescribed to treat. 88 it is unknown if myopathy is dose-dependent, although myotoxicity progression has been observed with prolonged treatment ( table 2 ). 89 thrombocytopenia, agranulocytosis, and disseminated intravascular coagulation have been reported with aminoquinoline use. 90 hemolytic anemia has also been reported with findings j o u r n a l p r e -p r o o f including jaundice, hemoglobinuria, and renal failure. 90, 91 in patients with glucose-6-phosphate dehydrogenase (g6pd) deficiency, hemolysis can occur due to free radical accumulation in erythrocytes. 91, 92 due to a lack of reduced glutathione, oxidative stress denatures heme, causing extravascular hemolysis. the extent of hemolysis depends on the drug, dose, and the degree of enzyme deficiency, leading to a range of asymptomatic to life-threatening hemolysis. 93 primaquine is more closely associated with g6pd-mediated hemolysis. although case report literature describes the finding in chloroquine and hydroxychloroquine use, the largest chart review to date examining these drugs in patients with g6pd noted no occurrence of hemolysis. 91, 92 gold-standard evidence such as randomized controlled trials, systematic reviews, or metanalyses for management of aminoquinoline toxicity do not currently exist in the literature. the following recommendations are based on published expert opinion from poison control centers and medical toxicologists, as well as frequent findings described in case report literature. consultation with a poison control center and/or medical toxicologist is recommended early in the management of these patients in the emergency department. aminoquinoline overdose produces toxicity ranging from mild to severe. unlike with chloroquine overdoses, there is no established lethal or toxic dose of hydroxychloroquine in adults, and management should be tailored to observed toxicity. 22 mild chloroquine toxicity in adults is defined as symptomatology occurring with suspected ingested dose <2 g, normal systolic blood pressure, and normal qrs (≤120 ms). 19 moderate chloroquine toxicity occurs with suspected ingested dose 2-4 g, normal systolic blood pressure, and normal qrs (≤120 ms). 19 severe chloroquine toxicity occurs with suspected ingested dose >4 g, hypotension, and qrs prolongation (>120 ms). 54 doses exceeding 5 g are highly associated with mortality due to arrhythmias and hypokalemia. 94 in the following sections, strategies for the emergency management of aminoquinoline intoxication will be addressed, including decontamination, pharmacotherapeutics, elimination j o u r n a l p r e -p r o o f methods, and emerging modalities (i.e. ecmo and ile). algorithmic application of these strategies to the categorization of mild, moderate, and severe toxicity is shown in figure 1 . overdose. hydroxychloroquine and chloroquine have high volumes of distribution and significant protein binding, complicating modalities for augmenting elimination. 11 although these drugs are ingested, patients should not receive emetics such as syrup of ipecac, as toxicity sequelae of seizures, altered mentation, dysrhythmias, and hypotension heighten risks of aspiration. 11 similarly, orogastric lavage has fallen out of favor due to the risks of aspiration. in cases of life threatening ingestion, orogastric lavage can be considered in patients presenting early following ingestion, within one hour. 41, 66 activated charcoal effectively absorbs aminoquinoline in the gastrointestinal tract with 95%-99% binding when administered in the first five minutes following ingestion. 97 as with other decontamination strategies, the use of activated charcoal will depend on patient presentation (i.e. those who are not nauseated or vomiting) and duration of intoxication. 11 while serum drug levels may be drawn, they are not readily available and therefore are not a practical measure to guide initial management of acute toxicity in the ed setting. 74 however, for inpatient treatment, early and serial measurements of blood chloroquine concentrations are more accurate compared to estimated oral ingestion for predicting cardiovascular severity of chloroquine poisonings. 98 hypokalemia is a marker of severity of toxicity in acute poisoning and must be carefully monitored and managed as intracellular shifts can reverse as acute toxicity resolves, with rapid onset of hyperkalemia. 11 potassium may be repleted cautiously in severe hypokalemia (<1.9 meq/l), and monitoring of potassium levels should occur regularly. while older studies indicate that hypokalemia may prolong survival, contemporary data favor potassium repletion, generally to >4 meq/l. 64 dysrhythmias resulting from electrolyte derangements including potassium should be rapidly but carefully corrected. 11 class ia, ic, and iii antiarrhythmics should be avoided as they may worsen conduction delays. 11 magnesium sulfate 2g iv over 10 minutes may be used for tdp treatment, but has an unclear role in prophylaxis for qt prolongation ≥500 ms. 100 20 if epinephrine fails to adequately raise mean arterial pressure, a second pressor such as norepinephrine or phenylephrine can be titrated to effect, though alpha agonists increase the effective refractory period and may increase the occurrence of arrythmias. 103, 104 if hypotension is due to myocardial depression rather than arterial vasodilation, these vasoactive medications may worsen cardiac output. 104 patients requiring additional vasopressor support beyond epinephrine and diazepam should receive close attention to hemodynamic parameters to ensure treatment efficacy. diazepam is used in the management of both hypotension and dysrhythmias in dosages of 2 mg/kg iv over 30 minutes, followed by 1 to 2 mg/kg/d for 2-4 days in severe cases. 51 the mechanism of diazepam in attenuation cardiotoxicity is believed to have a central antagonistic effect, anticonvulsant effect, antidysrhythmic effect and interaction inverse to aminoquinolines, and decrease aminoquinoline induced-vasodilation. 22, 105, 106 experimental use of diazepam in animal models of severe chloroquine overdose demonstrates improved systolic and diastolic arterial pressures, heart rate, urine volume, urinary excretion of chloroquine, and shortened qrs duration. 102, 107 no studies have compared efficacy between different benzodiazepines for treatment of acute aminoquinoline toxicity. with medication shortages or variation in ed pharmacy stock, another benzodiazepine may be substituted for treatment of seizures and for maintenance of sedation. gastrointestinal symptoms, such as nausea, vomiting, and diarrhea, can be found in mildly intoxicated patients and more severe overdoses. vomiting in early stages of intoxication may be due to direct irritant effects of aminoquinolines, and may be better managed with the decontamination strategies addressed above. nausea and vomiting can be treated symptomatically while avoiding qtc prolonging agents such as serotonin antagonists (ondansetron) and phenothiazines (promethazine, prochlorperazine). 108 antihistamine (meclizine) and dopamine receptor antagonist (metoclopramide) antiemetics may be safer options. there are currently no accepted treatments for quinine-induced ocular toxicity, but fundoscopic examination, visual field examination, and color testing are appropriate to assess injury ideally by an ophthalmologist. 19 hyperbaric oxygen has been used successfully in vision recovery, but causality was not established. 109 to address sodium channel, blockade sodium loading with sodium bicarbonate (nahco 3 ), sodium acetate, or hypertonic saline (3% nacl) may be used. 11 consideration should be given to the degree of cardiac toxicity and severity of hypokalemia if present, favoring use of sodium acetate or hypertonic saline to avoid worsening hypokalemia. the ph can be used as an indirect indicator of sodium load. when using nahco 3 , a bolus of 1-2 meq/kg is recommended, repeated as needed to terminate dysrhythmias or narrow qrs complex, then utilizing a nahco 3 infusion. 11 when using sodium acetate, 1 meq/kg body weight may be infused over 15-20 min as a bolus. 110 potassium should be closely monitored for intracellular shifting of potassium with j o u r n a l p r e -p r o o f development of clinically significant hypokalemia. hypertonic saline contains the same quantity of sodium in 97 meq as sodium bicarbonate in 50 meq. when using 3% nacl, a bolus of 2-4 meq/kg may be considered, and sodium levels should be closely monitored. 111 approximately 50% of chloroquine is excreted renally, and acute renal failure is possible following acute intoxication. 112 providers should anticipate the possibility of extended toxicity course in patients with acute and/or chronic renal failure. unfortunately, hemodialysis use has been reported as ineffective due to high protein binding and large volume of distribution intrinsic to the aminoquinolines. 112 case report evidence suggests hemodialysis efficacy can be augmented by use of ile. 22 there are multiple reports of veno-arterial ecmo to successfully treat aminoquinoline toxicity. 98, [113] [114] [115] [116] ecmo may be considered in severe toxicity refractory to standard supportive care and other therapies (i.e. escalation of epinephrine drip rate to > 3 mg/hr, persistent endorgan failure). one case report describes ecmo initiation on intensive care unit admission following a 9.5 g chloroquine ingestion (initial blood chloroquine concentration 6215 µg/l). the patient presented with altered mental status, left ventricular systolic dysfunction with a dyskinetic interventricular septum, and hypotension unresponsive to crystalloid fluid resuscitation as well as 3 mg/hour epinephrine infusion. the patient was weaned from vasopressors on day three, decannulated from ecmo on day four, extubated on day seven, and discharged on day ten with no neurological sequelae. 117 another case detailing ecmo use in a patient experiencing ventricular fibrillation following 12 g hydroxychloroquine overdose noted j o u r n a l p r e -p r o o f "spectacular improvement of hemodynamic parameters and electrocardiographic normalization at day one." 114 owing to the lipophilicity of aminoquinolines, there are several reports of successful outcomes following ile use. 22, 46, 118, 119 recommended ile treatment is 1.5 ml/kg lean body mass (~100ml in adults) as bolus over two to three minutes followed by 200 ml over 10-15 minutes. 22 if benefit is seen in vital signs and/or ecg parameter normalization, slower continuous infusion of ~0.25 ml/kg/min can be administered until resolution of toxicity. 119 combined ile, nahco 3 , and vasopressor support has been reported in profound hydroxychloroquine overdose of 40 g presenting with hypokalemia and refractory ventricular fibrillation with positive outcome. 22 protracted ile has been associated with dysfunction of ecmo circuits, though this is unlikely in short-term ile use (<24 hours continuous infusion), and case reports have described safe concomitant use of both modalities. 118 ,120 serum triglyceride levels may be monitored to guide ile extent of infusion, with ~1000 mg/dl as a lipid volume limit of efficacy. 121 given the wide publicity in the lay media regarding the use of aminoquinolines for covid-19 and trends in national poison control center data, a more current exploration of the acute management of aminoquinoline toxicity is necessary. this class of drugs has a narrow therapeutic range and a large variance in toxic dose from person to person. severe symptoms can occur with doses as small as 1.5 g with onset one to three hours post-ingestion. management of acute toxicity often occurs in the emergency department and should focus on hemodynamic figure 1 pharmacology of chloroquine and hydroxychloroquine a systematic review on the efficacy and safety of chloroquine for the treatment of covid-19 efficacy of hydroxychloroquine in patients with covid-19: results of a randomized clinical trial. medrxiv the trial of chloroquine in the treatment of corona virus disease 2019 (covid-19) and its research progress in forensic toxicology hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting sars-cov-2 infection in vitro treatment options for covid-19: the reality and challenges letter to stakeholders: do not use chloroquine phosphate intended for fish as treatment for covid-19 in humans nigeria records chloroquine poisoning after trump endorses it for coronavirus treatment france2020. 10. national poison data system (npds) bulletin covid-19 (hydroxychloroquine/chloroquine) american association of poison control centers treatment of hydroxychloroquine overdose annual report of the american association of poison control centers' national poison data system (npds): 36th annual report annual report of the american association of poison control centers' national poison data system (npds): 35th annual report annual report of the american association of poison control centers' national poison data system (npds): 34th annual report annual report of the american association of poison control centers' national poison data system (npds): 33rd annual report annual report of the american association of poison control centers' national poison data system (npds): 32nd annual report annual report of the american association of poison control centers' national poison data system (npds): 31st annual report annual report of the american association of poison control centers' national poison data system (npds): 30th annual report chloroquine and hydroxychloroquine toxicity treatment of severe chloroquine poisoning hydroxychloroquine overdose: toxicokinetics and management novel therapies for myocardial irritability following extreme hydroxychloroquine toxicity hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting sars-cov-2 infection in vitro chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases effects of chloroquine on viral infections: an old drug against today's diseases? chloroquine is a potent inhibitor of sars coronavirus infection and spread characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72 314 cases from the chinese center for disease control and prevention an interactive web-based dashboard to track covid-19 in real time chapter four -structural insights into coronavirus entry human coronaviruses oc43 and hku1 bind to 9-o-acetylated sialic acids via a conserved receptor-binding site in spike protein domain a sars-cov-2 cell entry depends on ace2 and tmprss2 and is blocked by a clinically proven protease inhibitor new insights on the antiviral effects of chloroquine against coronavirus: what to expect for covid-19? chloroquine for the 2019 novel coronavirus sars-cov-2 breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of covid-19 associated pneumonia in clinical studies hydroxychloroquine or chloroquine with or without a macrolide for treatment of covid-19: a multinational registry analysis. the lancet retraction-hydroxychloroquine or chloroquine with or without a macrolide for treatment of covid-19: a multinational registry analysis observational study of hydroxychloroquine in hospitalized patients with covid-19 chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (sars-cov-2) infection: preliminary safety results of a randomized, double-blinded, phase iib clinical trial (clorocovid-19 study) food and drug administration. remdesivir by gilead sciences: fda warns of newly discovered potential drug interaction that may reduce effectiveness of treatment massive hydroxychloroquine overdose toxicokinetics of hydroxychloroquine following a massive overdose pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases hydroxychloroquine is much less active than chloroquine against chloroquine-resistant plasmodium falciparum, in agreement with its physicochemical properties in: poisindex® system (electronic version) early treatment with intravenous lipid emulsion in a potentially lethal hydroxychloroquine intoxication cytochrome p450 2c8 and cyp3a4/5 are involved in chloroquine metabolism in human liver microsomes therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases pharmacokinetics of hydroxychloroquine and chloroquine during treatment of rheumatic diseases pharmacokinetics of chloroquine in renal insufficiency current and future use of chloroquine and hydroxychloroquine in infectious, immune, neoplastic, and neurological diseases: a mini-review cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature antimalarial drugs and glucose metabolism therapeutic trial of diazepam versus placebo in acute chloroquine intoxications of moderate gravity drugs that may cause or exacerbate heart failure association of qt-prolonging medications with risk of autopsy-defined causes of sudden death chloroquine cardiomyopathy-a review of the literature syncope following oral chloroquine administration in a hypertensive patient controlled on amlodipine hydroxychloroquine-induced cardiomyopathy cardiomyopathy related to antimalarial therapy with illustrative case report hydroxychloroquine cardiotoxicity presenting as a rapidly evolving biventricular cardiomyopathy: key diagnostic features and literature review hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment hypokalaemia related to acute chloroquine ingestion clinical features and management of poisoning due to antimalarial drugs persistent hypokalemia despite aggressive potassium replacement following a hydroxychloroquine overdose quinine-induced hypoglycemia hydroxychloroquine as a glucose lowering drug the hypoglycemic effect of chloroquine chloroquine induced parkinsonism cns adverse events associated with antimalarial agents. fact or fiction? drug saf specific influence of chloroquine on central respiratory mechanisms management of sodium-channel blocker poisoning: the role of hypertonic sodium salts treatment of acute chloroquine poisoning: a 5-year experience chloroquine ototoxicity: an idiosyncratic phenomenon. otolaryngol head neck surg hydroxychloroquine ototoxicity in a patient with rheumatoid arthritis hydroxychloroquine-induced seizure in a patient with systemic lupus erythematosus accidental hydroxychloroquine overdose resulting in neurotoxic vestibulopathy ascorbic acid prevents chloroquine-induced toxicity in inner glial cells hydroxychloroquine and chloroquine retinopathy: screening for drug toxicity revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy hydroxychloroquine retinopathy. eye (lond) drugs used in the chemotherapy of protozoal infection: malaria toxicity of anti-rheumatic drugs in a randomized clinical trial of early rheumatoid arthritis safety of disease modifying anti-rheumatic agents in rheumatoid arthritis patients with chronic viral hepatitis the devil's in the dosing: severe druginduced liver injury in a hydroxychloroquine-naive patient with subacute cutaneous lupus erythematosus and porphyria cutanea tarda antimalarial myopathy: an underdiagnosed complication? prospective longitudinal study of 119 patients hydroxychloroquine causes severe vacuolar myopathy in a patient with chronic graft-versus-host disease hydroxychloroquine-induced agranulocytosis in a patient with long-term rheumatoid arthritis side effects of chloroquine and primaquine and symptom reduction in malaria endemic area examination of hydroxychloroquine use and hemolytic anemia in g6pdh-deficient patients the global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis covid-19: therapeutics and their toxicities chloroquine poisoning. rapidly fatal without treatment activated charcoal for chloroquine poisoning blood concentrations are better predictors of chioroquine poisoning severity than plasma concentrations: a prospective study with modeling of the concentration/effect relationships effectiveness of sms 201-995, a synthetic, long-acting somatostatin analogue, in treatment of quinine-induced hyperinsulinaemia prevention of torsade de pointes in hospital settings: a scientific statement from the american heart association and the american college of cardiology foundation pharmacological treatment of acquired qt prolongation and torsades de pointes protective cardiovascular effects of diazepam in experimental acute chloroquine poisoning effects of catecholamines and diazepam in chloroquine poisoning in barbiturate anaesthetised rats proarrhythmic effects of intravenous vasopressors chloroquine, hydroxychloroquine and covid-19 interactions of chloroquine with benzodiazepine, γ-aminobutyric acid and opiate receptors experimental assessment of the protective activity of diazepam on the acute toxicity of chloroquine covid-19: therapeutics and their toxicities ocular quinine toxicity treated with hyperbaric oxygen sodium acetate as a replacement for sodium bicarbonate in medical toxicology: a review reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution the risk of antimalarials in patients with renal failure extracorporeal membrane oxygenation in the treatment of poisoned patients survival after massive hydroxychloroquine overdose assistance circulatoire extracorporelle percutanée dans les défaillances hémodynamiques aiguës graves : expérience monocentrique chez 100 patients consécutifs early extracorporeal membrane oxygenation for cardiovascular failure in a patient with massive chloroquine poisoning intravenous lipid emulsion for intentional chloroquine poisoning intravenous lipid emulsion use for severe hydroxychloroquine toxicity what are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient confusion about infusion: rational volume limits for intravenous lipid emulsion during treatment of oral overdoses j o u r n a l p r e -p r o o f stabilization with the use of early mechanical ventilation, diazepam, epinephrine, frequent ecgs, and repeated blood glucose monitoring, with early step-up to aggressive resuscitative measures including ecmo to support vital functions until the offending agent is metabolized and cleared. key: cord-268526-gh9sy7sl authors: hwang, sung yeon; yoon, hee; yoon, aerin; kim, taerim; lee, guntak; jung, kwang yul; park, joo hyun; shin, tae gun; cha, won chul; sim, min seob; kim, seonwoo title: n95 filtering facepiece respirators do not reliably afford respiratory protection during chest compression: a simulation study date: 2019-03-27 journal: am j emerg med doi: 10.1016/j.ajem.2019.03.041 sha: doc_id: 268526 cord_uid: gh9sy7sl background: n95 filtering facepiece respirators (n95 respirators) may not provide adequate protection against respiratory infections during chest compression due to inappropriate fitting. methods: this was a single-center simulation study performed from december 1, 2016, to december 31, 2016. each participant underwent quantitative fit test (qnft) of n95 respirators according to the occupational safety and health administration protocol. adequacy of respirator fit was represented by the fit factor (ff), which is calculated as the number of ambient particles divided by the number inside the respirator. we divided all participants into the group that passed the overall fit test but failed at least one individual exercise (partially passed group [ppg]) and the group that passed all exercises (all passed group [apg]). then, the participants performed three sessions of continuous chest compressions, each with a duration of 2 min, while undergoing real-time fit testing. the primary outcome was any failure (ff < 100) of the fit test during the three bouts of chest compression. results: forty-four participants passed the qnft. overall, 73% (n = 32) of the participants failed at least one of the three sessions of chest compression; the number of participants who failed was significantly higher in the ppg than in the apg (94% vs. 61%; p = 0.02). approximately 18% (n = 8) of the participants experienced mask fit failures, such as strap slipping. conclusions: even if the participants passed the qnft, the n95 respirator did not provide adequate protection against respiratory infections during chest compression. emergency departments (eds), the principal portals of entry into healthcare systems, are increasingly required to screen and treat patients with communicable infections [1, 2] . in 2015, a large outbreak of middle east respiratory syndrome (mers) coronavirus infection occurred after exposure to a single patient in an overcrowded ed of a hospital in south korea; several individuals, including healthcare workers (hcws), were infected [3, 4] . the world health organization and the u.s. centers for disease control and prevention recommend that hcws must use a particulate filtering facepiece respirator that is at least as protective as the national institute for occupational safety and health (niosh)certified n95 filtering facepiece respirator (n95 respirator) or its equivalent when treating patients with airborne infectious diseases [5, 6] . however, such facepiece respirators can provide protection only when the face seal fits tightly. therefore, fit testing is essential; a qualitative or quantitative approach must be used to identify respirators that best suit each individual [7, 8] . the quantitative fit test (qnft) objectively determines the adequacy of respirator fit by measuring leakage around the face seal using the respirator fit tester [9, 10] . this device measures the fit factor (ff) (the number of ambient particles divided by the number inside the respirator when simulating eight workplace activities). an overall ff !100 is considered the passing level [9] . however, although the overall ff may be !100, the ffs for individual exercises may be <100 (for example, during bending). cardiopulmonary resuscitation (cpr), a common ed procedure, generates infectious aerosols, and this is associated with an increased risk of pathogen transmission to hcws [11, 12] . some exercises for the conventional qnft mimic chest compression, which include bending at the waist and head up-and-down movement [9] . however, chest compression during cpr is significantly more dynamic and rapid than qnft exercises. therefore, it is unclear whether the protective effects of the n95 respirators will be maintained during chest compression particularly in those who failed at least one individual conventional qnft exercise. previously, shin et al. have evaluated the effects of movements during chest compression on the protective performances of various n95 respirators in the simulated setting [13] . they demonstrated that the ffs of certain respirators decreased during chest compression, thereby seriously compromising respiratory performance. no study has yet explored the stability of n95 respirators in a group that only partially 'passed' the qnft. thus, we compared the respirator failure (ff < 100) rates during chest compression between a partially passed group (the overall fit factor was adequate, but at least one specific exercise was failed; the ppg) and an all passed group (group that passed all exercises: the apg). this was a single-center simulation study that explored potential issues that may be encountered when wearing an n95 respirator during chest compression. the study was conducted in a laboratory in samsung medical center (a tertiary, universityaffiliated, referral hospital located in a large city in korea) from december 1, 2016, to december 31, 2016. the temperature and humidity of the room were controlled at approximately 23°c and 30%, respectively, to minimize the impact of environmental factors on outcomes. the institutional review board of our institution approved the study, and a written informed consent was obtained from each participant. the inclusion criteria were as follows: hcws aged !20 years, those certified for the delivery of basic life support or advanced cardiovascular life support by the american heart association (aha) or those who had completed our institutional training program, and those who delivered cpr in the clinical field [14] . the exclusion criteria were as follows: hcws who were pregnant, those with any musculoskeletal diseases that compromised the capacity to deliver chest compression, and those with medical conditions, including asthma, congestive heart failure, or coronary heart disease. moreover, the participants who failed the fit tests for all three respirators were not included. at the beginning of the simulation, the investigators conducted a brief training session for the participants, which included providing instructions for the overall flow of the study using slides and via demonstration and practice in using the standardized n95 respirator donning technique. they were instructed to complete questionnaires about the demographic characteristics of the participants after the training session. then, every participant took the qnft for the n95 respirator. we divided the participants into two groups (ppg and apg) (fig. 1 ). since the mers epidemic in 2015, all employees in our institution must be fit tested using three n95 respirators: the 1860 and 1870+ (3 m, st. paul, mn) and the 46,727 (kimberly clark, irving, tx). the best-fitting respirator is identified based on the qnft ff and comfort of the person who wears such device. we selected respirators based on earlier data available for all participants. however, if the shape of the face had changed because of weight change, plastic surgery, or dental correction, the fit test was repeated. we used the portacount pro+ 8038 respirator fit tester (tsi inc., shoreview, mn) for qnft. the qnft for the n95 respirator was conducted according to the occupational safety and health administration (osha) protocol [9, 15] . while wearing the respirator, eight test exercises were performed in the following order: normal breathing, deep breathing, head side-to-side moving, head up-and-down motion, talking, grimacing, bending over, and normal breathing. for the talking exercise, the participants read identical text prepared in advance. each exercise was performed for 1 min except for grimacing (15 s). the ff of grimacing was excluded from the final calculation according to the osha protocol [9] . an ff > 200 was scored as 200 by the tester. all ffs were continuously monitored and considered passing if the final score was !100. after the fit test, the participants were instructed to perform continuous chest compression on a resusci anne mannikin (laerdal medical, stavanger, norway) three times for 2 min each (with 4-min rest between each session) while undergoing further fit testing (fig. 1) ; they were not allowed to touch or adjust the mask. if the mask strap loosened, it was re-adjusted during the break. to ensure that the cpr was of high quality, which is in accordance with the 2015 aha guidelines, all data were collected using a laerdal pc skill reporting system (laerdal medical) [16] . one investigator provided feedback to all participants in real time while watching the computer monitor. the participants rested for 20 min after the three sessions of chest compression, followed by an additional compression for 2 min while wearing the same respirator after performing a user-seal-check. the primary outcome was any failure (ff < 100) of the fit test during the three bouts of chest compression. the secondary outcome was the slipping down of respirator during chest compression. a priori sample size calculations were made in terms of primary outcome achievement; we assumed an a value of 0.05 for twosided hypothesis testing and a b error of 0.20 (power = 80%). a preliminary study of 10 participants has revealed a failure rate of 50%. we considered that a 40 percentage point increase in the failure rate was clinically significant; we assumed that the ppg might evidence failure. a total of 42 patients were required to detect this hypothesized failure rate. standard descriptive statistics were used to present all data. continuous variables were provided as medians with interquartile ranges (iqrs), and the wilcoxon rank-sum test was used for comparisons. categorical data were presented as numbers with percentages and compared using the chi-square test. stata version 13.0 software (stata corporation, college station, tx) was used to perform all statistical analyses. we recruited 45 participants, of whom 1 was excluded due to failure in the baseline qnft using all three n95 respirators; 44 participants were ultimately included, of whom 66% (n = 29) were female. the median age of the participants was 31 (iqr: 26.5-36) years. most participants were nurses (52%, n = 23) with an average clinical experience of 6 (iqr: 3-10) years. baseline data, such as age, sex, career duration, body mass index, occupation, cpr training, and respirator type, did not significantly differ between the two groups ( table 1 ). the 3m 1870 + n95 respirator (n = 25, 57%) was most frequently used, followed by the kimberly clark 46727 (n = 15, 34%) and the 3m 1860 (n = 4, 9%). no significant differences were observed in the quality of chest compression between the two groups except in terms of compression rate during the second cycle (ppg vs. apg: 113.5, iqr: 109-116.5 vs. 108.5, iqr: 105-114, p = 0.04) ( table 2 ). the outcomes are shown in table 3 and fig. 2 . overall, 73% (n = 32) of the participants failed at least one of the three chest compression sessions; the failure rate was significantly higher in the ppg than in the apg (94 vs. 61%; p = 0.02). in total, 18% (n = 8) of the participants experienced respirator failure, such as strap loosening. the overall failure rate of the fit test after userseal-check was 59% (n = 26), and it was not different between the ppg and apg (63% vs 57%, p = 0.73). even when the participants passed the qnft, n95 respirators did not afford adequate protection during chest compression. notably, in 94% of the participants in the ppg, the ff decreased to <100 during at least one session of chest compression. facepiece respirators only work properly when the face seal is tight [17, 18] . body movements during chest compression are both dynamic and intense, and sweat further compromises respirator fit, creating a gap permitting disease transmission. therefore, our findings are clinically significant in terms of the safety of hcws who are at high risk for airborne disease transmission during chest compression even when wearing adequately fit-tested n95 respirators. the conventional qnft is widely used to measure n95 respirator performance in hcws. however, the exercises performed during the fit test are not similar to those executed in real-world setting. suen et al. have used a portable aerosol spectrometer to evaluate the performance of n95 respirators during various nursing procedures, including suction and nasogastric tube insertion for 10 min [19] . the average ff decreased significantly from 184.85 to 134.71 after completing the procedures, and the ff fell to <100 in 33% of the participants. this study indicated that n95 respirators may not provide consistent protection against respiratory infection for hcws. the qnft failure rates during chest compression after the user-seal-check did not differ between the two groups. several previous studies have suggested that this user-seal-check alone inadequately evaluates respirator fitting [20, 21] . nevertheless, in clinical practice, all treatments are performed after a user-sealcheck alone. therefore, our results suggest that pre-passing the n95 qnft did not ensure respiratory safety during chest compressions. it is known that the risk of disease transmission from patients to rescuers during cpr is extremely low [22, 23] . one review article has shown that the number of infections acquired during cpr is approximately <1/200,000 [24] . however, previous studies have data were presented as median with interquartile range or n (%). one retrospective cohort study has reported that one of nine hcws who participated in cardiac compression developed severe acute respiratory syndrome (sars) [25] . of the six hcws who performed cpr on a patient with mers, one acquired the infection [11] . experiences from the outbreaks of highly contagious diseases, such as sars and mers, taught us that hcws should be protected from airborne disease transmission when performing cpr [11, 12, 26, 27] . the current international cpr guidelines do not address the extent of airway protection required by hcws when performing cpr on patients with suspected or confirmed airborne diseases [22] . infection-prevention strategies for hcws tend to take second place in life-threatening situations requiring minimization of noflow time [11, 12] . however, the safety of hcws is in fact paramount. mechanical compression devices can be used to minimize hcw participation in cpr. in addition, hcws engaging in chest compression of patients with airborne diseases could wear powered air-purifying respirators with hoods (paprs) rather than n95 respirators. however, this may result in resuscitation difficulties, and both movement and communication are compromised [28, 29] . in addition, the protective effects of paprs during chest compression have not been explored, and further studies are warranted. our study had certain limitations. first, we aimed to maximally reflect actual clinical settings. however, we worked in a simulation laboratory, and the outcomes of the present study might differ from those of real-world settings. the participants performed continuous chest compression based on the assumption that the patient had an advanced airway. however, in patients without an advanced airway, chest compressions are briefly paused to provide ventilation [16] . cpr is complex, featuring chest compression, endotracheal intubation, defibrillation, bag-valve ventilation, intravenous line insertion, and drug administration. however, we focused on chest compression only. if the participants carried out other tasks, then the outcomes might have differed. in addition, in the present study, the participants were instructed not to talk as much as possible. we believed that such action was reasonable when providing cpr to patients with air-borne disease. however, hcws need to talk for communication in real settings, which can loosen the fitting of the n95 respirator. second, we had only three respirator types available; thus, our results cannot be generalized to other models. third, although chest compression lasted for 2 min, the ff was obtained after excluding data from the first 20 s because the time was used for ambient purge, ambient sample, and mask purge. even in individuals who passed the initial fit test, n95 respirators did not provide adequate protection during chest compression. the participants in the ppg were at particular risk of airborne disease transmission during chest compression. further study must be conducted to establish specific guidelines about the level of respiratory protection for hcws during cpr of patients with airborne diseases. none. a survey on infection control in emergency departments in japan the utility of preliminary patient evaluation in a febrile respiratory infectious disease unit outside the emergency department mers-cov outbreak following a single patient exposure in an emergency room in south korea: an epidemiological outbreak study middle east respiratory syndrome coronavirus superspreading event involving 81 persons guidelines for preventing health-care-associated pneumonia, 2003: recommendations of cdc and the healthcare infection control practices advisory committee infection prevention and control of epidemic-and pandemic-prone acute respiratory infections in health care. geneva: world health organization laboratory performance evaluation of n95 filtering facepiece respirators niosh guide to industrial respiratory protection occupational safety and health administration comparison of two quantitative fit-test methods using n95 filtering facepiece respirators healthcare worker infected with middle east respiratory syndrome during cardiopulmonary resuscitation in korea possible sars coronavirus transmission during cardiopulmonary resuscitation the plots represent the median fit factor with interquartile ranges of the baseline qnft and three sets of chest compression. qnft, quantitative fit test comparing the protective performances of 3 types of n95 filtering facepiece respirators during chest compressions: a randomized simulation study tsi incorporated. portacount ò pro 8030 and portacount ò pro+ 8038 respirator fit testers american heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care sars transmission among hospital workers in hong kong a quantitative assessment of the total inward leakage of nacl aerosol representing submicron-size bioaerosol through n95 filtering facepiece respirators and surgical masks reliability of n95 respirators for respiratory protection before, during, and after nursing procedures sensitivity and specificity of the userseal-check in determining the fit of n95 respirators fit characteristics of n95 filtering facepiece respirators and the accuracy of the user seal check among koreans european resuscitation council guidelines for resuscitation 2015: section 2. adult basic life support and automated external defibrillation american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care infections acquired during cardiopulmonary resuscitation: estimating the risk and defining strategies for prevention risk factors for sars transmission from patients requiring intubation: a multicentre investigation in toronto sars exposure and emergency department workers protecting health care workers from sars and other respiratory pathogens: a review of the infection control literature respiratory protection during simulated emergency pediatric life support: a randomized, controlled, crossover study sars safety and science the authors have no potential conflicts of interest or funding sources to declare. key: cord-333827-zpdnzwle authors: zhao, jinqiu; li, xiaosong; huang, wenxiang; zheng, junyi title: potential risk factors for case fatality rate of novel coronavirus (covid-19) in china: a pooled analysis of individual patient data date: 2020-08-17 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.039 sha: doc_id: 333827 cord_uid: zpdnzwle background and objective: since the first case of the pneumonia caused by 2019 novel coronavirus (covid-19) is found in wuhan, there have been more than 70,000 cases reported in china. this study aims to perform the meta-analysis of risk factors for the case fatality rate (cfr) of the 2019 novel coronavirus (covid-19). design and methods: we have searched pubmed, google scholar and medrxiv for the cohort studies involving risk factors for the cfr of covid-19. this meta-analysis compares the risk factors of cfr between fatal patients and non-fatal patients. results: two cohort studies are included in this study. after comparing the patients between fatal cases and non-fatal cases, several important factors are found to significantly increase the cfr in patients with covid-19, and include the age ranging 60–70 (or = 1.85; 95% ci = 1.62 to 2.11; p < .00001) and especially≥70 (or = 8.45; 95% ci = 7.47 to 9.55; p < .00001), sex of male (or = 1.88; 95% ci = 1.30 to 2.73; p = .0008), occupation of retirees (or = 4.27; 95% ci = 2.50 to 7.28; p < .00001), and severe cases (or = 691.76; 95% ci = 4.82 to 99,265.63; p = .01). as the advancement of early diagnosis and treatment, the cfr after january 21 (or 22), 2020 is substantially decreased in covid-19 than before (or = 0.21; 95% ci = 0.19 to 0.24; p < .00001). conclusions: several factors are confirmed to significantly improve the cfr in patients with covid-19, which is very important for the treatment and good prognosis of these patients. sarbecovirus, orthocoronavirinae subfamily), and has some similar features of severe acute respiratory syndrome coronavirus (sars-cov) [6] . covid-19 is highly thought to be associated with huanan seafood wholesale market and delivered to humans from wild animals illegally sold [8] . according to the first 425 confirmed ncip in wuhan from december 2019 to january 2020, the epidemiologic characteristics confirmed human-to-human transmission among close contacts since the middle of december 2019 and revealed that the epidemic was doubled in size every 7.4 days in the early stage [3] . the human-to-human transmission of ncip was also confirmed by case reports and family settings [9] [10] [11] [12] . the novel coronavirus was found in stool samples of patients with abdominal symptoms, indicating that fecal-oral transmission might occur for ncip [13] . some studies have helped understand the molecular, clinical and epidemiological features of the covid-19 [6, 14, 15] . one cohort study conducted in jin yin-tan hospital (wuhan, china) first reported the epidemiological, clinical, laboratory and radiological characteristics, as well as clinical outcomes in 41 ncip patients [16] . the clinical features mainly include fever, cough, dyspnea, myalgia, fatigue, sputum production, headache, haemoptysis, and diarrhoea [17, 18] . kidney injury and even death [16, 22] . some severe patients with covid-19 resemble that of sars-cov [8, 16] . another cohort study also systematically reported the epidemiological and clinical features of 138 patients with ncip in zhongnan hospital of wuhan university (wuhan, china) [18] . nonpharmaceutical interventions such as shutdown of public gathering places, wearing of facial masks and social distancing are still effectively slow the spread of the disease. there is currently no antiviral treatment or vaccine specifically designed for this virus with field-proven effectiveness, and supportive therapies are mainly used for these patients [23] . there have been more than 2, 000 deaths in china. this meta-analysis is conducted to reveal the risk factors for cfr in patients with covid-19, which is valuable to improve the treatment and prognosis of these patients. ethical approval and patient consent were not required because this was a meta-analysis of previously published studies. two investigators independently searched the following databases (inception to february 20 2020): pubmed, google scholar, medrxiv and cnki. the electronic search strategy was performed using with the following keywords: -novel coronavirus‖ or -covid-19‖, and -epidemiological‖ or -clinical features‖ or -clinical characteristics‖ or -death‖ or -case fatality rate‖ or -cfr‖. the following inclusive selection criteria were applied: (i) patients were diagnosed with 2019 novel coronavirus diseases (covid-19) (ii) study design was the j o u r n a l p r e -p r o o f journal pre-proof cohort study comparing fatal patients with non-fatal patients (or severe cases versus non-severe cases). we used a piloted data-extraction sheet, and collected the following information: publication year, first author, number of patients, age, gender and the number of non-severe/severe cases in two groups. data were extracted independently by two investigators. this meta-analysis focused on the risk factors including baseline characteristics and severity on the cfr of covid-19. furthermore, the risk factors that would be analyzed should be compared in both of two included studies. odds ratio (or) with 95% confidence intervals (ci) was used for all dichotomous outcomes. the random-effects model was used regardless of heterogeneity which was assessed by i 2 statistic. i 2 > 50% indicated significant heterogeneity [24] . sensitivity analysis was needed when encountering significant heterogeneity. p<0.05 suggested statistically significance between two groups. all analysis were conducted using review manager version 5.3. a detailed flowchart of the search and selection results is shown in figure 1 . one hundred potentially relevant articles were identified initially, and two cohort studies involving 48,666 patients are finally included in this study [23, 25] . two studies that the data collected is from information system for infectious disease reporting through february 11 th , 2020 [25] . the main characteristics (e.g. age, gender and severity of patients) of the two cohort studies are presented in table 1 . after carefully analyzing the two studies, age, sex, occupation and severity are selected for the association with cfr of covid-19. two studies revealed that severe cases are significantly older than those non-severe cases [17, 18] [17] . these indicate that old age may also result in the increase in cfr in these patients. the association analysis between age range with cfr is revealed in figure 2 . the age≤50 (or=0.07; 95% ci=0.06 to 0.10; p<0.00001) and ranging 50~60 (or=0.50; 95% ci=0.42 to 0.60; p<0.00001) is associated with obviously relatively lower incidence of cfr, while the age ranging 60~70 (or=1.85; 95% ci=1.62 to 2.11; p<0.00001) and especially≥70 (or=8.45; 95% ci=7.47 to 9.55; p<0.00001) results in the significant increase in cfr. these results suggest that age≥60 can be regarded as the risk factor for cfr in patients with covid-19. j o u r n a l p r e -p r o o f in this study, we mainly find the association between sex and cfr of these patients ( figure 3 ). this meta-analysis indicates that the sex of female is associated with relatively lower incidence of cfr (or=0.53; 95% ci=0.37 to 0.77; p=0.0008), while the sex of male leads to the obvious increase in cfr for covid-19 (or=1.88; 95% ci=1.30 to 2.73; p=0.0008). the cdc study reported five kinds of occupation, including service industry, farmer/worker, medical worker, retiree, and others [25] . in order to perform the analysis between occupation with cfr, service industry, farmer/worker, and medical worker are generally regarded as employed persons, while others are generally thought to be unemployed persons. in our meta-analysis between occupation with cfr (figure 4) it is widely accepted that severe cases receive intensive care unit (icu) care, the time periods are generally divided into three periods: before january 10 (or 14), 2020, after january 21 (or 22), 2020 and the middle time period between them. in our meta-analysis ( figure 6 ), the cfr before january 10 (or 14), 2020 is relatively high (or=5.14; 95% ci=1.74 to 15.15; p=0.003), but the cfr is significantly reduced after january 21 (or 22), 2020 (or=0.21; 95% ci=0.19 to 0.24; p<0.00001). the transmissibility of covid-19 is similar to that of sars-cov in the range of 2.9-3.3% [23] . the overall adjusted cfr is estimated to be 3.06% for the covid-19, which is lower than those of sars-cov (9.2%) and mers-cov (34.4%) [20] . one included study demonstrates that patients in icu group is significantly older than those in non-icu group (66 (57-78) versus 51 (37-62), median (iqr), p<.001) [18] , which is consistent with the study conducted by guan et al [17] . furthermore, the old age limit ≥65 years may be defined as the risk factor for exacerbation of covid-19 (p<0.001) [17] . our results reveal that age ranging 60~70 age and especially≥70 is found to have notably increased cfr in these patients, and thus age≥70 can be regarded as the important risk factor for increased crf. in addition, retirees are revealed to have improved cfr than other occupations of j o u r n a l p r e -p r o o f journal pre-proof patients with covid-19 in this meta-analysis, which may be attributed to older age of retirees. patients with low immune function such as old age, obesity, presence of comorbidity, hiv infection, long-term use of immune-suppressive agents and pregnant women may have improved cfr [26] . prompt administration of antibiotics to prevent infection and immune support treatment may reduce the complications and cfr of these patients [8] . the reduced lymphocytes was found in most patients, suggesting that 2019-ncov may mainly damage lymphocytes, especially t lymphocytes, which was similar to sars-cov. substantially decreased t lymphocytes might be an important factor for predicting the exacerbations of patients [27] . a descriptive study reported 99 cases of ncip from wuhan jinyintan hospital from jan 1 to jan 20, 2020, and demonstrated that older men with comorbidities was more likely to suffer from ncip and ards. [8] . in contrast, the proportion of men and women showed no statistical difference between icu patients and non-icu patients in another study [18] . there are conflicting results regarding the relationship between sex and severity of covid-19. in this meta-analysis, male patients have significantly virus acts mainly through binding to ace2 receptors, which may account for the gender difference [28] . it is generally known that severe cases and patients receiving icu have higher possibility of death than other patients for diseases. one cohort study involving 1099 patients reported 14 deaths in 173 severe cases (8.1%) and 1 death in 926 non-severe cases (0.1%), and significant difference of cfr is observed between severe cases and non-severe cases [17] . these results are also confirmed in this meta-analysis. severe cases with covid-19 have increased cfr than non-severe cases. regarding the sensitivity analysis, there is significant heterogeneity for occupation, severity and time period. several reasons may account for this heterogeneity. firstly, in the analysis of cdc study, service industry, farmer/worker, and medical worker are generally regarded as employed persons, while others are generally thought to be unemployed persons [25] , which may produce the heterogeneity for occupation. secondly, one study reported the mild pneumonia/non-pneumonia versus severe pneumonia [23] , while the cdc study reported the mild cases versus severe/critically ill cases [25] , and thus there is lack of clear definition of non-severe versus severe cases, which may cause the heterogeneity for severity analysis. thirdly, different patient populations in the three time periods are selected in two studies, which may explain the heterogeneity for the analysis of time periods. fourthly, these two studies are retrospective trials, which also produce some heterogeneity. one study also confirmed that the patients in icu group had more comorbid diseases than those patients in non-icu group [18] . older age and comorbidity may j o u r n a l p r e -p r o o f journal pre-proof be risk factors for the exacerbation of ncip [8] . furthermore, the comorbid diseases such as cardiovascular diseases, copd and hypertension may also increase the cfr in covid-19 patients. existing antiviral treatments such as lopinavir/ritonavir and remdesivir have been evaluated and used for treating sars-cov and mers-cov infections [29, 30] . they are also considered for the treatment of covid-19 infections [21] . clinical trials with large patient sample should be carefully designed and implemented to assess their efficacies. this meta-analysis has several potential limitations. firstly, there are only two retrospective cohort studies included, and more studies with larger sample should be conducted to investigate this issue. secondly, there is significant heterogeneity for occupation, severity and time period, which may be caused by different definition of occupation, severe cases and different patient population in the three time periods. thirdly, there may be some repetitive data in these two studies, which may have some influence on the pooling results. fourthly, there may be some confounding relationship between the occupation of retiree and age, but it is not available to adjust the occupation of the retiree by age based on current limited data. in conclusion, this study reveals the several factors including age≥60, sex of male, occupation of retirees and severe cases can substantially increase the cfr in patients with covid-19. these findings are of crucial importance for timely treatment and good prognosis of these patients. huang conducted the study planning, data analysis and data interpretation, junyi zheng and junyi zheng wrote and revised the article. all authors read and approved the final manuscript. all relevant data are within the manuscript. medical university (pyjj2019-06, https://www.cqmu.edu.cn/) and natural science foundation of chongqing(cstc2019jcyj-msxmx0281, http://www.csti.cn/govwebnew /). zjq conducted the study design, data collection and analysis, decision to publish, and preparation of the manuscript. we declare no conflict of interest. the association analysis between age with cfr. the association analysis between sex with cfr. the association analysis between occupation with cfr. the association analysis between severity with cfr. the association analysis between time period with cfr. the continuing 2019-ncov epidemic threat of novel coronaviruses to global health-the latest 2019 novel coronavirus outbreak in wuhan, china coronavirus infections-more than just the common cold early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia outbreak of pneumonia of unknown etiology in wuhan china: the mystery and the miracle transmission and epidemiological characteristics of novel coronavirus (2019-ncov)-infected pneumonia (ncip): preliminary evidence obtained in comparison with 2003-sars, medrxiv a novel coronavirus from patients with pneumonia in china genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster importation and human-to-human transmission of a novel coronavirus in vietnam transmission of 2019-ncov infection from an asymptomatic contact in germany nowcasting and forecasting the potential domestic and international spread of the 2019-ncov outbreak originating in wuhan, china: a modelling study the digestive system is a potential route of 2019-ncov infection: a bioinformatics analysis based on single-cell transcriptomes, biorxiv the 2019-new coronavirus epidemic: evidence for virus evolution clinical characteristics of 2019 novel coronavirus infection in china clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in the first case of 2019 novel coronavirus pneumonia imported into korea from wuhan, china: implication for infection prevention and control measures a novel coronavirus outbreak of global health concern first case of 2019 novel coronavirus in the united states a novel coronavirus (2019-ncov) causing pneumonia-associated respiratory syndrome epidemiological and clinical features of the 2019 novel coronavirus outbreak in china quantifying heterogeneity in a meta-analysis the epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (covid-19) in china clinical features of three avian influenza h7n 9 virus-infected patients in s hanghai t-cell immunity of sars-cov: implications for vaccine development against mers-cov single-cell rna expression profiling of ace2, the putative receptor of wuhan 2019-ncov role of lopinavir/ritonavir in the treatment of sars: initial virological and clinical findings comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against mers-cov none. all authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs). not applicable. not applicable. not applicable. the authors declare no conflict of interest. not applicable. jinqiu zhao and xiaosong li conducted the design, junyi zheng and wenxiang huang key: cord-333176-6v7ficfk authors: snell, jonathan title: sars-cov-2 infection and its association with thrombosis and ischemic stroke: a review covid-19, thrombosis, and ischemic stroke date: 2020-09-30 journal: am j emerg med doi: 10.1016/j.ajem.2020.09.072 sha: doc_id: 333176 cord_uid: 6v7ficfk this review of current literature provides background to the covid-19 pandemic, as well as an examination of potential pathophysiologic mechanisms behind development of thrombosis and ischemic stroke related to covid-19. sars-cov-2 infection is well-documented to cause severe pneumonia, however, thrombosis and thrombotic complications, such as ischemic stroke, have also been documented in a variety of patient demographics. sars-cov-2 infection is known to cause a significant inflammatory response, as well as invasion of vascular endothelial cells, resulting in endothelial dysfunction. these factors, coupled with imbalance of ace2 and ras axis interactions, have been shown to create a prothrombotic environment, favoring thromboembolic events. ischemic stroke is a severe complication of covid-19 and may be a presenting symptom in some patients. coronaviruses are positive-sense single stranded rna viruses of the coronaviridae family. 1 the genome of coronaviruses contains open reading frames for 16 non-structural sars-coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov). 1 zoonotic origin in southern china and leading to over 8,000 confirmed cases with an estimated 9-11% fatality rate. 1,2 mers-cov is currently endemic to the arabian peninsula and has proven to be a dangerous virus of zoonotic origin with an estimated 36% fatality rate. 1 december 2019 marked the discovery of a new coronavirus in wuhan, china after an outbreak of severe pneumonia of unknown origin. 3 isolation and sequencing of this virus from human airway epithelial cells allowed the characterization of the betacoronavirus named sars coronavirus 2 (sars-cov-2) that is the etiologic agent of coronavirus disease 2019 (covid19) . 3, 4 further characterization of sars-cov-2 has demonstrated close genomic similarity to several types of bat coronavirus, indicating bats as a likely reservoir for this virus of zoonotic origin. 4 sars-cov-2 shares approximately 79% sequence identity with sars-cov, though sars-cov-2 has demonstrated a higher rate of transmission than sars-cov. 4 basic reproductive number (r 0 ) is used to represent the transmissibility of a disease and is defined the average number of new cases caused by a single infective person in an unexposed population. 5 the r 0 of sars-cov-2 and sars-cov are estimated at 2.9 and 1.85 for each virus, respectively. 5,6 this is likely due to the presence of asymptomatic or mildly symptomatic transmission of sars-cov-2, and its current prevalence in the human population supports the infective potential of this novel coronavirus. 5, 6 since its december 2019 emergence, sars-cov-viral entry into cells by coronaviruses is mediated through the interaction between a cellsurface receptor protein and the viral s-protein. 9 cellular tropism of coronaviruses is dependent on the s-protein-receptor interaction 9 and understanding the tropism of sars-cov-2 is the beginning to elucidating the myriad effects this virus may have on human physiology. sars-cov-2 shares 73% to 76% amino acid sequence identity in the receptor binding domain of its s-protein with sars-cov 4,10 , and the amino acid sequence directly interacting with the cell receptor is highly conserved between the viruses. 4,10 sars-cov has been previously determined to use the human transmembrane protein angiotensin converting enzyme 2 (ace2) as its receptor for viral entry, and sars-cov-2 had been speculated to use ace2 for viral entry as well. 9, 10 several studies have confirmed that ace2 is the functional receptor for sars-cov-2. 11, 12, 13 ace2: its location and role in the renin-angiotensin system (ras) human ace2 is a transmembrane zinc metalloprotease that acts as a carboxypeptidase in the metabolic degradation of angiotensin i and angiotensin ii (angii). 14 ace2 mrna is expressed in most tissues of the body, with highest expression in the gi tract, kidney, testes, heart, and lungs. 15 ace2 protein is found expressed on the surface of lung alveolar epithelial cells, enterocytes of the small intestine, arterial smooth muscle cells, and both arterial and venous endothelial cells, including intracranial vessels. 16 while soluble ace2 exists after cleavage of ace2 from the apical cell surface, it plays little to no physiologic role. 16 ace2 primarily catalyzes the conversion of angii into angiotensin-(1-7) (ang1-7), a metabolite that opposes the actions of angii and the ras axis through activation of the mas receptor. 17 generation of ang1-7 can take a more circuitous route through ace2 catalyzation of angiotensin i into angiotensin-(1-9) followed by ace catalyzation of angiotensin-(1-9) into j o u r n a l p r e -p r o o f journal pre-proof increased circulating levels of ang1-7 have been demonstrated to lower blood pressure, improve endothelial function, and attenuate the effects of angii in spontaneously hypertensive rats. 17 additionally, ang1-7 administered to spontaneously hypertensive rats treated with a nitric oxide synthase inhibitor attenuated the inhibitor's effects on map, as well as demonstrated cardioprotective effects in the setting of global cardiac ischemia. 18 ace2 and ang1-7 play an essential physiologic role in vasodilation and regulation of endothelial function in opposition to the effects of angii. figure 1 summarizes the production of angii and ang1-7, as well as their effects. imbalance of ace and ace2 products has the potential to cause significant dysfunction and has been implicated as playing a role in the pathogenesis of sars. 19 downregulation of ace2 expression has been demonstrated after sars-cov pulmonary and myocardial infection 19, 20 and is linked to the acute pulmonary injury seen in sars. 19 hypercoagulability in sars-cov-2 infection covid-19 symptomology is diverse, including shortness of breath, cough, and fatigue with many cases progressing into pneumonia requiring oxygen therapy. 21 covid-19 patient developed immune thrombocytopenic purpura after heparin treatment was begun. 34 heparin treatment was ceased after thrombocytopenia developed, though antibody testing for antiplatelet factor 4 and antiplatelet antibodies was negative. 34 these events suggest sars-cov-2 infection as the precipitating event for the thrombocytopenia in this case, though causative studies are necessary. the complement system has also been implicated in the pathophysiology of sars-cov-2 infection. a series of patients with severe covid-19 were determined to have significant deposits of terminal complement proteins and signs of systemic complement activation were present. 35 complement was also co-localized with sars-cov-2 s-protein in these patients, indicating complement targeting of virally-infected endothelium. 35 previous studies of complement activation in sars-cov infection indicated endothelial dysfunction as the source of complement activation, and murine c3 protein knockout models demonstrated less severe infection with sars-cov. 36 activation of the complement system has the potential to increase the risk of thrombus formation, both through c3a stimulation of platelets and insertion of terminal complement components into membranes. 37 imbalance of the interactions between ace2 and the ras axis may also contribute to the thromboembolic events seen in sars-cov-2 infection. ang1-7, the major product of ace2, and angii have competing effects on blood pressure and endothelial activation: where angii serves to increase blood pressure and activate the endothelium, ang1-7 reverses these actions j o u r n a l p r e -p r o o f journal pre-proof through the mas receptor ( figure 1 ). 17,38 ang1-7 has also been shown to decrease thrombus formation through the production of nitric oxide and prostacyclin by both platelets and endothelial cells. [39] [40] [41] this is contrasted by the actions of angii, which has been shown to accelerate thrombus formation through induction of tissue factor production and generation of free radicals that scavenge free nitric oxide. 42, 43 downregulation of ace2 by sars-cov-2 infection 20 may result in an imbalance of these systems, leading to predisposition to thromboembolic events. cerebrovascular events can be a significant consequence of uncontrolled thrombotic states, and represent a global burden to both quality of life and national economics. 44, 45 ischemic stroke due to occlusion of large arteries has been a documented complication of sars-cov infection in patients with minimal to no risk factors. 46 sars-cov-2 infection seems to also increase risk of developing ischemic stroke, among other neurological consequences. 78 of 214 patients in a retrospective case series of hospitalized patients in wuhan, china demonstrated nervous system dysfunction (cns, peripheral nervous system, and/or skeletal muscle dysfunction). 47 of these 78 patients, 6 developed ischemic strokes; 5 of these patients had been categorized as severe covid-19 and 1 had been categorized as non-severe. 47 unexplained encephalopathic features in 13 of 58 patients were seen in another case series of covid-19 patients. 48 ischemic stroke was diagnosed in 3 of these 13 patients (2 small acute and 1 sub-acute strokes). 48 genetic recombination, and pathogenesis of coronaviruses a novel coronavirus from patients with pneumonia in china genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding the reproductive number of covid-19 is higher compared to sars coronavirus transmission dynamics of 2019 novel coronavirus (2019-ncov). social science research network centers for disease control and prevention who director-general's opening remarks at the media briefing on an overview of their replication and pathogenesis receptor recognition by the novel coronavirus from wuhan: an analysis based on decade-long structural studies of sars coronavirus a pneumonia outbreak associated with a new coronavirus of probable bat origin structure, function, and antigenicity of the sars-cov-2 spike glycoprotein sars-cov-2 cell entry depends on ace2 and tmprss2 and is blocked by a clinically proven protease inhibitor a human homolog of angiotensin-converting enzyme cloning and functional expression as a captopril-insensitive carboxypeptidase quantitative mrna expression profiling of transgenic angiotensin-converting enzyme 2 overexpression in vessels of shrsp rats reduces blood pressure and improves endothelial function angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with l-name a crucial role of angiotensin converting enzyme 2 (ace2) in sars coronavirus-induced lung injury sars-coronavirus modulation of myocardial ace2 expression and inflammation in patients with sars clinical characteristics of coronavirus disease 2019 in china clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet incidence of thrombotic complications in critically ill icu patients with covid-19 upsurge of deep venous thrombosis in patients affected by covid-19: preliminary data and possible explanations abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. the lancet fibrinolysis shutdown correlation with thromboembolic events in severe covid-19 infection severe acute respiratory syndrome and venous thromboembolism in multiple organs the clinical pathology of severe acute respiratory syndrome (sars): a report from china endothelial cell infection and endotheliitis in covid-19 endothelial dysfunction: a marker of atherosclerotic risk interactions between the innate immune and blood coagulation systems coagulopathy and antiphospholipid antibodies in patients with covid-19 immune thrombocytopenic purpura in a patient with covid-19 complement associated microvascular injury and thrombosis in the pathogenesis of severe covid-19 infection: a report of five cases will complement inhibition be the new target in treating covid-19-related systemic thrombosis? links between complement activation and thrombosis the ace2/angiotensin angiotensin 1-7 and mas decrease thrombosis in bdkrb2−/− mice by increasing no and prostacyclin to reduce platelet spreading and glycoprotein vi activation an orally active formulation of angiotensin-(1-7) produces an antithrombotic effect the antithrombotic effect of angiotensin-(1-7) involves mas-mediated no release from platelets roles of coagulation and fibrinolysis in angiotensin ii enhanced microvascular thrombosis prothrombotic effects of angiotensin epidemiology and the global burden of stroke human and economic burden of stroke large artery ischaemic stroke in severe acute respiratory syndrome (sars) neurologic manifestations of hospitalized patients with coronavirus disease stroke in a young covid -19 patient surprise diagnosis of covid-19 following neuroimaging evaluation for unrelated reasons during the pandemic in hot spots covid-19-related strokes in adults below 55 years of age: a case series large-vessel stroke as a presenting feature of covid-19 in the young prothrombotic state induced by covid-19 infection as trigger for stroke in young patients: a dangerous association. eneurologicalsci severe acute respiratory syndrome coronavirus 2 infection and ischemic stroke key: cord-290684-3f6prlqy authors: duan, jun; chen, baixu; liu, xiaoyi; shu, weiwei; zhao, wei; li, ji; li, yishi; hong, yueling; pan, longfang; wang, ke title: use of high-flow nasal cannula and noninvasive ventilation in patients with covid-19: a multicenter observational study date: 2020-07-29 journal: am j emerg med doi: 10.1016/j.ajem.2020.07.071 sha: doc_id: 290684 cord_uid: 3f6prlqy background: the use of high-flow nasal cannula (hfnc) and noninvasive ventilation (niv) in patients with covid-19 is debated. methods: this study was performed in four hospitals of china from january to march 2020. we retrospectively enrolled 23 and 13 covid-19 patients who used hfnc and niv as first-line therapy, respectively. results: among the 23 patients who used hfnc as first-line therapy, 10 experienced hfnc failure and used niv as rescue therapy. among the 13 patients who used niv as first-line therapy, one (8%) used hfnc as rescue therapy due to niv intolerance. the duration of hfnc + niv (median 7.1, iqr: 3.5–12.2 vs. 7.3, iqr: 5.3–10.0 days), intubation rate (17% vs. 15%) and mortality (4% vs. 8%) did not differ between patients who used hfnc and niv as first-line therapy. in total cohorts, 6 (17%) patients received intubation. time from initiation of hfnc or niv to intubation was 8.4 days (iqr: 4.4–18.5). and the time from initiation of hfnc or niv to termination in patients without intubation was 7.1 days (iqr: 3.9–10.3). among all the patients, c-reactive protein was independently associated with intubation (or = 1.04, 95% ci: 1.01–1.07). in addition, no medical staff got nosocomial infection who participated in hfnc and niv management. conclusions: in critically ill patients with covid-19 who used hfnc and niv as first-line therapy, the duration of hfnc + niv, intubation rate and mortality did not differ between two groups. and no medical staff got nosocomial infection during this study. at the end of 2019, a new coronavirus, now named severe acute respiratory syndrome coronavirus 2 (sars-cov-2), was first isolated at wuhan, china [1] . the coronavirus causes a cluster of acute respiratory illness, now named coronavirus disease 2019 (covid-19) [2] . it has been demonstrated that the most dangerous feature of covid-19 was person-to-person transmission [3] . with the spread of the epidemic, many countries have reported confirmed cases associated with sars-cov-2. on march 11, 2020, the world health organization (who) declared the outbreak of covid-19 was a global pandemic. in the covid-19 population, 14% of the patients were categorized as severe cases and 5% as critical cases [4] . a systematic review and meta-analysis has pooled 31 articles involving 46959 cases with covid-19 and reported that the incidence of icu admission was 29.3% [5] . at the early stage, the high-flow nasal cannula (hfnc) or noninvasive ventilation (niv) was used in 24% of hospitalized patients [2] . and in the critical ill patients, the use of hfnc and niv was 31% and 37%, respectively [6] . in lombardy region, italy, the niv was used in 11% of icu patients [7] . in seattle region, usa, the hfnc was used in 42% of critically ill patients [8] . however, these studies failed to report how the hfnc or niv was used. here, we aimed to report the clinical features, settings and outcomes of hfnc and niv in patients with j o u r n a l p r e -p r o o f medical center). in the suspected patients, the real-time reverse transcription polymerase chain reaction (rt-pcr) assay was performed according to the guideline made by our national health commission [9] . the covid-19 was confirmed by a positive rt-pcr. all the patients with a confirmed covid-19 were candidates to our study. we enrolled all the patients who used hfnc or niv as first-line therapy. among the hfnc patients, 17 cases extracted from a previous study were secondarily analyzed [10] . this study was approved by the local ethics committee and institutional review board (the first affiliated hospital of chongqing medical university, no. 20200201). given its observational nature, informed consent was waived. the application of niv and hfnc was in the negative pressure ward or intensive care unit (icu). to protect the medical staff, the n95 respirator, eye protection (mask with a visor), disposable gown, disposable surgical gloves, and disposable shoe covers were provided. before entering the ward, all the medical staffs had wore these devices and checked each other. niv was managed according to current guidelines and the experts' suggestions [11] [12] [13] [14] . face mask was the first choice to delivery the niv to the patients. optimal size of the mask was selected based on the face type in each patient. hearted humidification was provided to improve oral or nasal dryness. the initial continuous positive airway pressure (cpap) or positive end expiratory pressure (peep) was 4 cmh 2 o. when the patient tolerated this pressure, it was gradually increased to improve the oxygenation. the initial inspiratory pressure was 8-10 cmh 2 o. j o u r n a l p r e -p r o o f hfnc was managed also based on current consensus and the experts' suggestions [13] [14] [15] . the temperature was set between 31 and 37 °c, the flow was set between 30 and 60 l/min, and the fio 2 was set to maintain the spo 2 more than 93%. when the hfnc failed to maintain the oxygenation or relieve dyspnea, the niv as a rescue therapy was an alternative if the patient did not require urgent intubation. when the respiratory distress was relieved and the oxygenation was improved, the intermittent use of niv or hfnc was performed. we gradually increased the time of conventional oxygen therapy and shortened the duration of hfnc or niv until it was totally weaned. when the respiratory distress and oxygenation progressively deteriorated, intubation for invasive mechanical ventilation was performed based on the criteria made by our society of critical care medicine [16] . however, the intubation was decided at the discretion of the attending physicians. before the use of hfnc or niv, the demographics, vital signs, laboratory tests and the arterial blood gas tests were collected. the baseline pao 2 /fio 2 was measured with the use of conventional oxygen therapy before the use of hfnc or niv. we estimated the fio 2 as follows: fio 2 (%) = 21+4*fow (l/min) [17] . using these data, the acute physiology and chronic health evaluation ii (apache ii) score and sequential organ failure assessment (sofa) score were calculated. data were analyzed by statistical software (spss 17.0; ibm corp., armonk, ny). student's t test was used to analyze the normally distributed continuous variables and mann-whitney u test was used to analyze the non-normally distributed continuous variables. chi-squared test or fisher's exact test was used to analyze the categorical variables. variables with a p value <0.1 in univariate analyses were entered into logistic regression analyses to identify independent risk j o u r n a l p r e -p r o o f factors associated with intubation. the ability to predict intubation was tested by the area under the receiver operating characteristic curve (auc). the value at maximum youden index was selected as optimal cutoff value [18] . a p value < 0.05 was considered significant. among all the enrolled patients, 35 cases were in the negative pressure ward and one was in the icu. among them, hfnc was used as first-line therapy in 23 patients and niv in 13 patients ( figure 1 ). the clinical characteristics of the hfnc and niv patients were summarized in table 1. the mean age was 65 ± 14 years in hfnc group and 50 ± 14 years in niv group (p ＜0.01). the proportion of male was 52% in hfnc group and 92% in niv group (p =0.03). there were no differences in disease severity, the proportion of comorbidity, and the level of oxygenation between the two groups. patients in hfnc group had higher chlorine, low alanine aminotransferase (alt) and lower total bilirubin than that in niv group. others laboratory tests were no differences between the two groups. table 2 shows the settings of the hfnc and niv at the initial 24 h. in hfnc group, the temperature was around 35℃, flow was around 40 l/min, and fio 2 was around 40%. in there were no differences in vital signs and arterial blood gas tests between hfnc and niv groups except the respiratory rate (table 3) . at 1-2 h, 12 h and 24 h, the respiratory rate was lower in hfnc group than that in niv group. the outcomes between the two groups were summarized in table 4. in hfnc group, 10 (43%) patients used niv as a rescue therapy. in niv group, one (8%) used hfnc due to niv intolerance. there was no difference in the duration of hfnc + niv between the patients who used hfnc and niv as first-line therapy (median 7.1 days, iqr: 3.5-12.2 vs. 7.3 days, iqr: 5.3-10.0, p =0.67). there was also no difference in intubation rate (17% vs. 15%, p ＞0.99) and mortality (4% vs. 8%, p ＞0.99) between the two groups. among all the patients, 6 received intubation and 30 avoided intubation (table 5 ). in multivariate analyses, only c-reactive protein was independently associated with intubation ( table 6 ). the auc for prediction of intubation was 0.92 (95% confidence interval [ci]: 0.77-0.98) ( figure 2 ). using c-reactive protein of 59 mg/l as cutoff value to predict intubation, the sensitivity was 100% and specificity was 79%. in addition, no medical staff got nosocomial infection in our study. nearly half of the patients who used hfnc as first-line therapy were transitioned to niv as a rescue therapy. however, only fewer patients who used niv as a first-line therapy were transitioned to hfnc. the intubation rate and mortality were relatively low. the duration of hfnc + niv, intubation rate and mortality did not differ between the two groups. among all the patients, c-reactive protein was independently associated with intubation. and it had high distinguishing power to predict intubation. in china, use of hfnc ranged from 21% to 31% (pooled incidence: 26%) among the critically ill patients, and the use of niv ranged from 14% to 37% (pooled incidence: 28%) [6, 19, 20] . however, the use of hfnc and niv were largely different between china and other countries. in lombardy region, italy, niv was used in 11% of icu patients but no patients used hfnc [7] . in seattle region, usa, the hfnc was used in 42% of critically ill patients but none used niv [8] . maybe, the availability of the hfnc and niv, and suggestions or recommendations made by experts or consensus were various between different countries. in china, the experts have suggested that the hfnc and niv can be used in covid-19 patients with pao 2 /fio 2 ≥150 mmhg, and niv can be cautiously used in those with pao 2 /fio 2 between 100 and 150 mmhg [13, 14] . the asian critical care clinical trials group has suggested that the hfnc and niv only can be used in covid-19 patients with mild acute respiratory distress syndrome (ards) [21] . the surviving sepsis campaign covid-19 subcommittee (most of the experts came from european and usa) has suggested that the hfnc is superior to niv in covid-19 patients with acute hypoxemic respiratory failure, and the niv can be tried with close monitoring if the hfnc is unavailable [22] . however, most of the recommendations were based on the experts' suggestion. the level of evidence is weak. to the best of our knowledge, there were no studies to focus on the use of hfnc or niv in covid-19 patients except our previous one paper [10] . different with the experts' suggestions, 10 patients (17% in hfnc and 46% in niv) with pao 2 /fio 2 between 100 and 150 mmhg have used hfnc or niv as a first-line therapy. and among all the patients, the duration of hfnc + niv, intubation rate and mortality were similar between two groups. these data provide an important reference for clinical physicians to select respiratory support device on patients with covid-19. among all the patients who used niv as first-line therapy, the intubation rate was 92% in patients with middle east respiratory syndrome, 30% in patients with severe acute respiratory syndrome, and 59% in patients with influenza pneumonia [23] [24] [25] . in hypoxemic patients whose respiratory failure caused by other reasons, the intubation rate was 36% [26] . however, in our study, the intubation rate was only 15% in covid-19 patients who used niv as a first-line intervention. among the patients who used niv as a rescue therapy, the intubation rate was 20%. and no medical staff in our study was infected by the airborne transmission. therefore, the niv is an alternative respiratory support for covid-19 patients but all safety measures should be taken. early identification of the high-risk patients and early application of intubation decreased mortality [27] . on the contrary, delayed intubation significantly lead to mortality increase both in patients with hfnc and niv [28, 29] . in our study, we found that the c-reactive protein collected at the initiation of hfnc or niv had high distinguishing power to predict intubation. therefore, hfnc and niv should be cautiously used in patients with high level of c-reactive protein. close monitoring should be taken to avoid delayed intubation. fear of aerosolized transmission was the major problem during the use of hfnc or niv in covid-19 patients. in theory, niv generates more aerosols than hfnc as niv usually generates higher pressure than hfnc [30] . in our study, use of hfnc and niv was in the negative pressure ward or icu, adequate protective supplies (n95 respirator, eye protector, disposable gown, j o u r n a l p r e -p r o o f peep/cpap, cmh 2 o 6 (6-9) 6 (6-9) 6 (6-10) j o u r n a l p r e -p r o o f hfnc = high flow nasal cannula, niv = noninvasive ventilation, apache ii = acute physiology and chronic health evaluation ii; sofa = sequential organ failure assessment, alt = alanine aminotransferase, ast = aspartate aminotransferase, *p <0.05 for comparison between patients with and without intubation j o u r n a l p r e -p r o o f a novel coronavirus from patients with pneumonia in china clinical features of patients infected with 2019 novel coronavirus in wuhan, china early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72314 cases from the chinese center for disease control and prevention imaging and clinical features of patients with 2019 novel coronavirus sars-cov-2: a systematic review and meta-analysis clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study baseline characteristics and outcomes of 1591 patients infected with sars-cov-2 admitted to icus of the lombardy region covid-19 in critically ill patients in the seattle the experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of chongqing clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting official ers/ats clinical practice guidelines: noninvasive ventilation for acute respiratory failure critical care committee of chinese association of chest physician. [conventional respiratory support therapy for severe acute respiratory infections (sari): clinical indications and nosocomial infection prevention and control respiratory support for severe 2019-ncov pneumonia suffering from acute respiratory failure: time and strategy respiratory & critical care medicine group of chinese thoracic society society of critical care medicine of chinese medical association respiratory care equipment index for rating diagnostic tests clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study covid-19 with different severity: a multi-center study of clinical features intensive care management of coronavirus disease 2019 (covid-19): challenges and recommendations surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (covid-19) noninvasive ventilation in critically ill patients with the middle east respiratory syndrome effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome early non-invasive ventilation treatment for severe influenza pneumonia noninvasive ventilation failure in patients with hypoxemic respiratory failure: the role of sepsis and septic shock assessment of heart rate, acidosis, consciousness, oxygenation, and respiratory rate to predict noninvasive ventilation failure in hypoxemic patients failure of high-flow nasal cannula therapy may delay intubation and increase mortality non-invasive ventilation in community-acquired pneumonia and severe acute respiratory failure exhaled air dispersion during high-flow nasal cannula therapy versus cpap via different masks key: cord-301623-uza6gu4r authors: moscarelli, alessandra; iozzo, pasquale; ippolito, mariachiara; catalisano, giulia; gregoretti, cesare; giarratano, antonino; baldi, enrico; cortegiani, andrea title: cardiopulmonary resuscitation in prone position: a scoping review date: 2020-09-10 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.097 sha: doc_id: 301623 cord_uid: uza6gu4r introduction: the ongoing pandemic of covid-19 brought to the fore prone positioning as treatment for patients with acute respiratory failure. with the increasing number of patients in prone position, both spontaneously breathing and mechanically ventilated, cardiac arrest in this position is more likely to occur. this scoping review aimed to summarize the available evidence on cardiopulmonary resuscitation in prone position (‘reverse cpr’) and knowledge or research gaps to be further evaluated. the protocol of this scoping review was prospectively registered on 10th may 2020 in open science framework (https://osf.io/nfuh9). methods: we searched pubmed, embase, medline and pre-print repositories (biorxiv and medrxiv) for simulation, pre-clinical and clinical studies on reverse cpr until 31st may 2020. results: we included 1 study on manikins, 31 case reports (29 during surgery requiring prone position) and 2 nonrandomized studies describing reverse cpr. no studies were found regarding reverse cpr in patients with covid-19. conclusions: even if the algorithms provided by the guidelines on basic and advanced life support remain valid in cardiac arrest in prone position, differences exist in the methods of performing cpr. there is no clear evidence of superiority in terms of effectiveness of reverse compared to supine cpr in patients with cardiac arrest occurring in prone position. the quality of evidence is low and knowledge gaps (e.g. protocols, training of healthcare personnel, devices for skill acquisition) should be fulfilled by further research. meanwhile, a case-by-case evaluation of patient and setting characteristics should guide the decision on how to start cpr in such cases. this scoping review aimed to summarize the available evidence on the cardiopulmonary resuscitation in prone position ("reverse cpr") and to highlight possible knowledge or research gaps to be further evaluated. for the purpose of this review, we searched pubmed, embase, and medline for preclinical and clinical studies on prone cpr. our search included the keywords "resuscitation", "cpr", "chest compression", "cardiopulmonary", "resuscitation", "prone position" as exact phrases and a combination of broad subject headings according to databases syntax. specifically, the embase engine was used with the following query: a search was also conducted on main pre-print repositories (biorxiv and medrxiv) from inception to 31st may 2020 for relevant studies. no limitations were imposed for specific contexts, with the aim of including surgical, medical and intensive care settings. articles on animals or on manikins were also eligible. randomized controlled trials (rcts), nonrandomized studies (both prospective or retrospective), case series and case reports were included. abstracts and conference proceedings were excluded. snowballing search on the references of selected articles was also performed. after the exclusion of duplicates and abstracts, two authors (am, pi) independently screened full-text papers to include the most relevant on the topic and independently charted data using an electronic standardized form. in case of case reports or series j o u r n a l p r e -p r o o f describing more than one patient, we collected data only on patients meeting inclusion criteria (i.e. cardiac arrest occurring in prone position and cpr performed). we collected data regarding the type of study (e.g. design and country), population characteristics at baseline (e.g. age, main disease), setting (e.g. operatory room, icu), occurred events (e.g. rhythm and cause of the cardiac arrest), intervention (e.g. prone or standard cpr) and outcomes (e.g. mortality, return of spontaneous circulation -rosc). data were then tabulated for presentation, as appropriate. the protocol of this scoping review was prospectively registered on 10 th may 2020 (https://osf.io/nfuh9). the scoping review was conducted following prisma statement extension for scoping reviews [8] . the initial search identified 1301 results from embase, pubmed and other sources. following screening of titles and abstracts and removing duplicates, we evaluated 82 articles in full text. among these, we selected and included 34 articles. the search from pre-print repositories (biorxiv and medrxiv) resulted in 52 records screened, none included. the details on the inclusion/exclusion process are provided in the prisma flow diagram (see fig.1 ). we found no rct comparing prone to standard supine cpr. three of the included studies [9] [10] [11] had a nonrandomized design and 31 were case reports [12, 13, [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] 14, [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] 15, 42, [16] [17] [18] [19] [20] [21] . in this section, the included nonrandomized studies are described; a complete description of all the studies, including case reports, is provided with details in table 1 . the first study evaluating the feasibility of reverse cpr was a simulation study using laerdal "resuscianne" manikins, posed in prone position on a standard examination j o u r n a l p r e -p r o o f coach, with a gel pad under the sternum. thirty-six trained nurses were asked to perform 100 compressions on the manikin with no breaks for respirations. using a skillmeter, a total of 3376 compressions (91.8% of the 3600 total possible) were registered, but only 1168 (34.6%) were effective (4 -5 cm compression depth), with 1370 (40.6%) partially effective (2 -4 cm compression depth) and 838 (24.6%) ineffective (< 2 cm compression depth) compressions. only 9/36 nurses were able to perform 70% or more adequate compressions (usually considered as the acceptable threshold). an important insight was provided by the authors, discussing that all the nurses had judged cpr in the prone position as more tiring than in the standard position. this, in addition to the light weight of the manikin and the position of the nurses (left-hand side of the manikin), may explain the low rate of successful compressions and the number of compressions performed off the midline (11.2% to the right of midline, 4.1% too high, 6.1% too low, none to the left of the midline). none of the eligible studies were conducted on animals. among the nonrandomized studies on humans, one was conducted on 11 cadavers and 10 healthy volunteers, evaluating indirect outcomes (blood pressure and tidal volume) [9] . mean arterial pressure (map) was invasively measured in cadavers both during standard and consecutive back chest compressions (55 ± 20 / 13 ± 7 vs. 79 ± 20 / 17 ± 10 p=0.028) performed at a rate of 60 per minute. healthy volunteers" tidal volume was then measured using a mouthpiece connected to a spirometer, while they were receiving back chest compressions (60 min -1 ). spontaneous breathing was held, and a nose clip applied on the volunteers. mean registered tidal volume was of 399 ± 110 ml. the authors highlighted that their findings may support prone cpr in non-intubated patients, since airways open spontaneously, and adequate ventilation seems achievable with compressions only. nonetheless, the study has limited external validity, especially for the finding regarding tidal volume (e.g. possibly not generalizable to patients with a compromised pulmonary function), requiring further investigations. another nonrandomized study enrolled six icu patients in cardiac arrest, after the declared failure of standard cpr [10] . main results included a systolic blood pressure mean improvement of 23 ± 14 mmhg, a calculated map mean improvement of 14 ± 11 mmhg and a diastolic blood pressure mean improvement of 10 ± 12 mmhg from standard to reverse cpr, but no cases of rosc. despite such a limited basis, we retrieved a total of 31 case reports described in literature from 1982 (date of the first retrieved report) to date, for a total of 34 patients. among the included case reports, 29 described cardiac arrests occurred during surgery. surgeries included spinal surgery in 20 patients (e.g. discectomies, scoliosis correction, vertebral metastases), craniotomy in 10 patients (e.g. primitive or metastatic cancer, hemorrhage), and cases of pelvic fracture and dorsal lipoplasty. one occurred in the icu [33] in a prone positioned mechanically ventilated patient, admitted for community acquired pneumonia and acute respiratory failure. another article reported a case of cardiac arrest during endoscopic retrograde cholangiopancreatography procedure [22] . no studies were found regarding reverse cpr in patients with covid-19. the feasibility of cpr in prone position has been under investigated. its use has been described in the settings of both operatory rooms (e.g neurosurgery, orthopedics) and icus (e.g. mechanically ventilated patients with respiratory failure), mainly on case reports. the main finding of this scoping review is that there is insufficient evidence on the topic and further evidence is needed, considering that an increasing number of cardiac arrests in prone position are expected during the covid-19 pandemic. j o u r n a l p r e -p r o o f many aspects, both decisional and technical, have been described but remain controversial and need to be investigated with adequately designed studies. to date, evidence on reverse cpr comes from case reports and small sized nonrandomized studies conducted on manikins, cadavers, healthy volunteers or patients with previously failed standard cpr. among the included reports, rosc after reverse cpr occurred in 23 out of 31 cases, demonstrating that the technique may be effective and deserves further investigations. nevertheless, publication bias may exist, potentially overestimating the rate of favorable outcomes in prone cpr, and potentially limiting our findings. we did not find any rct on the topic and nonrandomized studies only provide preliminary and indirect data to support the technique. despite prone cpr may be a feasible and safe option in specific settings, further literature is needed, with many aspects remaining uninvestigated. from the evaluated articles, it can be argued that a frequent cause of cardiac arrest in prone position is air embolism, a potentially fatal event, often occurring in neurosurgery and closely related to the position of the patient and the presence of a pressure gradient allowing air flow into the vessels. other causes are linked with the specific patient positioning, which can sometimes lead to vessel occlusion and reduced venous return. hypovolemia in combination with reduced venous return can quickly lead to reduced cardiac output. the rhythm presentation is various, ranging from asystole to pulseless electrical activity (pea), or ventricular fibrillation (vf) . in the event of a cardiac arrest in a prone positioned patient, the clinicians have limited time to decide whether to turn the patient into supine position, before starting cpr, or immediately start a reverse cpr. there is no clear evidence of superiority in terms of effectiveness of reverse compared to supine cpr in patients with cardiac arrest occurring in prone position. thus, clinicians should take into account several factors when deciding how to start cpr in such cases. turning the patient into supine position before starting cpr could be very difficult for several reasons: i) this maneuver is time consuming, and can potentially increase the no-flow time to the brain; ii) it may need at least 3-4 operators, not always available in surgical or icu settings; iii) it could be dangerous for the patients, due to the presence of an open wound, protruding metal work, an unstable spine and fixed head to a mayfield skull clamp potentially causing neurologic injuries, or iv) it could cause the dislodgment of the endotracheal tube and the loss of monitoring. furthermore, the decision to perform supination and proceed with a standard cpr entails other risks, such as a difficult hemorrhage control (e.g. during spinal surgery) [30] . on the other hand, healthcare personnel might be reluctant to perform reverse cpr as a first option, especially due to the lack of specific training and knowledge of the procedure. other concerns may regard the presence of an open surgical field, the limited surface to perform compressions, the need for a counterforce under the sternum and the risks of spinal damages. notwithstanding, cardiac massage in this position is less likely to cause rib fractures, injury to the heart and aspiration pneumonia [9] . since 2005, the american heart association (aha) guidelines for cpr and emergency cardiovascular care recommended that cpr in the prone position might be reasonable when the patient cannot be replaced in the supine position without prejudice, particularly in hospitalized patients with an advanced airway in place [1] . j o u r n a l p r e -p r o o f aha interim guidance for cpr in patients with covid-19 recommends to attempt to place in the supine position for continued resuscitation of patients with suspected or confirmed covid-19 who are in a prone position without an advanced airway, and to avoid turning the patient to the supine position if an advanced airway is secured, unless able to do so without risk of equipment disconnections and aerosolization [7] . similar recommendations are also supported by the european resuscitation council (erc) in its covid-19 guidelines [43] , suggesting to turn patient supine in case of ineffective compressions (arterial line and aim for diastolic pressure greater than 25 mmhg), airway problems or unrestored circulation (after minutes) [43] . a recent joint position statement from brazilian societies of cardiology, intensive care medicine, anesthesiology and emergency medicine recommends to turn into supine position the patients once safely possible, due to insufficient evidences on reverse cpr and suggests monitoring using partial pressure of end-tidal carbon dioxide partial (etco 2 >10mmhg) and diastolic pressure (>20mmhg) [44] . an early planning of supination is recommended, since it may require additional help [30, 44] . for the specific setting of neurosurgery, uk resuscitation council suggests that there is no immediate need to turn the patient to the supine position once cardiac arrest has occurred in the prone position, suggesting to start cpr in the prone position [45] . if the aforementioned techniques are not rapidly feasible or become unsuccessful, thoracotomy and direct internal cardiac massage and/or defibrillation are available options [30] . once a cardiac arrest is detected in a prone positioned patient, first of all it is important to make sure that airway is secured and the tube is not kinked, obstructed or displaced, in case of intubated patients. then, it is needed to ensure that the ventilator is connected to the patient with 100% fio 2 concentration and that there is no unidentified j o u r n a l p r e -p r o o f loss of blood [12] . if venous air embolism is suspected, the patient"s head should stay down, to increase venous pressure, and the surgical field should be flooded with saline. after that, chest compressions should be started. unfortunately, only general indications are provided by the guidelines on how to perform cardiac massage in prone position [46] . some are provided in aha recent interim guidance for patients with covid-19 [7] , erc provides some other practical indications [43] , suggesting compressing between the scapulae (shoulder blades) at the usual depth and rate (5 to 6 cm at 2 compressions per second) and placing defibrillator pad in anterior-posterior (front and back) or bi-axillary (both armpits) position (fig. 2) . alternatively, defibrillator pads can be applied in posterolateral position [29] , i.e. one pad in the left mid-axillary line and a second one over the right scapula, or over the left scapula (fig. 2) [19] . the effectiveness of reverse cpr also depends on the greater strength of thoracic costovertebral joints as compared to sternal costochondral junction and on the absence of abdominal contents displaced anteriorly and dissipating the compression force [15] . compressions. an option involves the use of two hands together at the midline at the midthoracic level (fig. 3, panel a) . if sternal support is present, rescuer"s hands can be placed on either side of the eventual incision at the midthoracic level, with the palms placed over the patient"s scapulae, thus preserving the sterility of the surgical field (fig. 3, a one-handed technique can be performed without sternal supports, with the flat of one hand (or with the hand clinched into a fist) on the lower third of the sternum used as counter pressure and the second one on the thoracic spine, and could be performed by one or two physicians (fig. 3, panel c) [33] . in the pediatric population cardiac massage can be started in the prone position using the fingers of one hand over the thoracic vertebral column at the level of the scapulae [35] with the same rate and force as they were delivered during supine position. the covid-19 pandemic represents a new challenge for clinicians in many fields, meanwhile, the available cpr guidelines should be followed. reverse cpr has been performed and described in several settings, but evidence is based on case reports and preliminary small sized nonrandomized studies. the procedure has been described in settings such as neurosurgery and prone position mechanical ventilation, and an increasing number of cardiac arrests in prone positioned patients is expected in the covid-19 era. the quality of available evidence is low and knowledge gaps should be fulfilled by further adequately designed studies that are urgently needed. meanwhile, a case-by-case evaluation of patient and setting characteristics should guide the decision on how to start cpr in such cases. american heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care european resuscitation council guidelines for resuscitation use of extreme position changes in acute respiratory failure helmet continuous positive airway pressure and prone positioning: a proposal for an early management of covid-19 patients feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to covid-19 (pron-covid): a prospective cohort study covid-19 kills at home: the close relationship between the epidemic and the increase of out-of-hospital cardiac arrests interim guidance for basic and advanced life support in adults, children, and neonates with suspected or confirmed covid-19 prisma extension for scoping reviews (prisma-scr): checklist and explanation cardiopulmonary j o u r n a l p r e -p r o o f journal pre-proof resuscitation in prone position: a simplified method for outpatients reverse cpr: a pilot study of cpr in the prone position the efficacy of cardiopulmonary resuscitation in the prone position prone cardiopulmonary resuscitation in elderly undergoing posterior spinal fusion with laminectomy cardiac arrest in the prone position caused by central venous cannulation-induced cardiac tamponade cardiac pulmonary resuscitation in prone position. the best option for posterior fossa neurosurgical patients cpr in prone position during neurosurgery venous air embolism during removal of bony spur in a child of split cord malformation air embolism during posterior spinal fusion in a 10-year-old girl: a case report cardiac arrest after epidural anesthesia for a esthetic plastic surgery: a case report cardiac arrest during craniotomy in prone position cardiopulmonary resuscitation in the prone position prone cpr for transient asystole during lumbosacral spinal surgery fatal air embolism during endoscopic retrograde cholangio-pancreatography (ercp): a case report venous air embolism: an unusual complication of atlantoaxial arthrodesis: case report erfolgreiche kardiopulmonale reanimation in bauchlage case studies of near misses in clinical anesthesia unsuccessful cardiopulmonary resuscitation during neurosurgery: is the supine position always optimal? cardiac arrest during desflurane anaesthesia in a patient with duchenne"s muscular dystrophy successful defibrillation in the prone position cardiac arrest during surgery and ventilation in the prone position: a case report and systematic review a case of ventricular fibrillation in the prone position during back stabilisation surgery in a boy with duchenne"s muscular dystrophy two cases of fatal air embolism in children undergoing scoliosis surgery cardiopulmonary resuscitation in the prone position: kouwenhoven revisited non-invasive continuous haemodynamic and petco 2 monitoring during peroperative cardiac arrest cardiac arrest and resuscitation of a 6-month old achondroplastic baby undergoing neurosurgery in the prone position intraoperative cardiopulmonary resuscitation in the prone position efficacit du massage cardiaque externe chez une patiente en ddcubitus ventral successful cardiopulmonary resuscitation of two patients in the prone position using reversed precordial compression venous air embolism during lumbar laminectomy in the prone position: report of three cases intraoperative death during lumbar discectomy sitting or prone? another argument for the latter fatal air embolism in an adolescent with duchenne muscular dystrophy during harrington instrumentation education: european resuscitation council covid-19 guidelines posicionamento posicionamento para ressuscitação cardiopulmonar de pacientes com diagnóstico ou suspeita de covid-19-2020 management of cardiac arrest during neurosurgery in adults prone cardiopulmonary resuscitation: a rapid scoping and expanded grey literature review for the covid-19 pandemic and 838 (24.6%) ineffective reid et al. (1998) [31] case report key: cord-318188-baat9464 authors: park, soo hyun; hwang, sung yeon; lee, guntak; park, jong eun; kim, taerim; shin, tae gun; sim, min seob; jo, ik joon; kim, seonwoo; yoon, hee title: are loose-fitting powered air-purifying respirators safe during chest compression? a simulation study date: 2020-03-31 journal: am j emerg med doi: 10.1016/j.ajem.2020.03.054 sha: doc_id: 318188 cord_uid: baat9464 background: the application of appropriate personal protective equipment for respiratory protection to health care workers is a cornerstone for providing safe healthcare in emergency departments. we investigated the protective effect and usefulness of loose-fitting powered air-purifying respirators (paprs) during chest compression. methods: this was a single-center simulation study performed from may 2019 to july 2019 in a tertiary hospital. we measured the concentrations of ambient aerosol and particles inside the loose-fitting papr during chest compression, and this ratio was set as the simulated workplace protecting factor (swpf). according to the national institute for occupational safety and health regulations, the assigned protection factor (apf) of loose-fitting paprs is 25. thus, the loose-fitting paprs were assumed to have a protective effect when the swpf were ≥ 250 (apf × 10). we measured the swpf of papr in real time during chest compression and also investigated the problems encountered during its use. results: ninety-one participants (median age 29 [interquartile range (iqr): 26–32] years; 74% female) completed the simulation. none of the participants failed with swpf below 250 during three sessions of chest compression. the median (iqr) values of swpf at three cycles were 17,063 (10,145-26,373), 15,683 (9477-32,394), and 16,960 (7695-27,279). there was no disconnection of equipment or mechanical failures during chest compression. in addition, most participants (83%) replied that they rarely or never experienced difficulty in verbal communication and felt that the loose-fitting papr was comfortable. conclusions: the loose-fitting paprs provided sufficient respiratory protection without disturbances during chest compression. in modern medicine, infection prevention and control measures are of central importance to the safety of patients, healthcare workers (hcws), and the community [1] . emergency departments (eds) are the principal portals of entry into healthcare systems, and the appropriate use of personal protective equipment (ppe) is one way to further reduce the risks of infection transmission [2, 3] . the severe acute respiratory syndrome (sars) and the middle east respiratory syndrome coronavirus (mers-cov) outbreaks have recently raised concerns of airborne transmission in the healthcare settings [4] [5] [6] . the world health organization (who) has recommended the use of particulate filtering facepiece respirators such as n95 filtering facepiece respirator (n95 respirator) or their equivalent when hcws treat patients with airborne infectious diseases, but facepiece respirators only work properly when the face seal is tight [1] . cardiopulmonary resuscitation (cpr) is a life-saving procedure that is frequently performed in the ed. chest compressions, one of the main components of cpr, needs intense and dynamic movements. previously published simulation studies showed that the n95 respirator did not provide adequate protection during chest compression [7] . according to the national institute for occupational safety and health (niosh) regulations, powered air-purifying respirators (paprs) are specified for high-hazard procedures (e.g., sputum induction, bronchoscopy, administration of aerosolized medication), because they can offer higher assigned protection factors (apfs) ranging from 25 to 1000 than n95 respirators (apf = 10) [8] . a papr is a batterypowered blower that provides clean air through a canister or cartridge american journal of emergency medicine xxx (xxxx) xxx with filter to the different type of hoods such as tight-fitting respirator, a loose-fitting hood, or a helmet. in the medical environment, loosefitting papr is mainly used because it can cover the entire face including the eye and it also does not require a fit test [9, 10] . to date, there are no standardized recommendations in the international cpr guidelines for the level of protective equipment that hcw should wear during cpr when treating patients with airborne diseases. since 2015, the korea centers for disease control and prevention (kcdc) has revised its guidelines for patients with suspected mers to use papr during cpr [11] . however, there is insufficient evidence on whether loose-fitting paprs provides and maintains a protective effect for hcws during cpr. in addition, because papr is a multi-piece equipment with external connections through an unfixed tube, there are concerns about the possibility of equipment problems such as tube disconnection and fan malfunction due to intense movements during chest compression. finally, papr may affect the satisfaction and performance of participants who perform chest compression. the purpose of this study was to investigate the protective effect of loose-fitting paprs during chest compressions. we also evaluated the user experience of the participants and the presence of any device problems. this was simulation study in a single center from may 2019 to july 2019. the study was conducted in an isolated room located in the ed which has identical conditions to manage patients with infection in samsung medical center (a tertiary hospital located in seoul, a capital city of south korea). temperature and humidity were controlled at approximately 23°c and 30%, respectively. the institutional review board of our institution approved the study, and a written informed consent was obtained from each participant. hcws who met all the following criteria were eligible for inclusion: 1) 20 years of age or older; 2) those certified for the delivery of basic life support or advanced cardiovascular life support by the american heart association (aha) or korean association of cardiopulmonary resuscitation, or those who had completed our institutional training program for cpr. participants with conditions that could cause harm to their health due to chest compressions such as pregnant, having asthma, coronary heart disease, and musculoskeletal diseases were excluded from the study. investigators briefly explained to the participants the entire simulation process (fig. 1) . the resusci anne manikin (laerdal medical, stavanger, norway) was used for the chest compressions. the participants were familiar with this manikin because it is used for regular cpr training of hcws in our institution. subsequently, all participants were trained on how to use papr. they checked the components of papr, connected the equipment, and practiced donning and doffing in equipment. participants completed a questionnaire to collect data on their demographic characteristics. the papr equipment used in this study consisted of a jupiter powered air turbo, breathing tube (bt-20 l) and loose-fitting hood (s-433 l-5) (3 m, st. paul, mn) (fig. 2) . the manufacturer's recommended air flow rate of the jupiter powered air turbo is between 150 l/min and 230 l/min; thus, we maintained the flow above 170 l/min in accordance with the niosh guidelines for loosefitting papr [10] . this equipment was certificated by the british standards institution (bsi), 539745 ce. the papr includes a particle filter p3 to protect against particles, including highly toxic materials. during the simulation, we used a rechargeable battery (5.2 v, nimh) that lasted 8 h when fully charged. the participants checked the operational state of the papr themselves including the filter's fitting status and flow test under supervision of the investigators. in order to pass the flow test, the ball in the cylinder had to rise above a specific line defined by the manufacturer. only the device that passed the test was used for the simulation. after flow test, they were equipped with the papr and confirmed that there is no problem in operation for 2 min. if any abnormality was found in operation, the equipment was readjusted or changed. the niosh has published and enforced apf for respiratory protective equipment. the apf means the workplace level of respiratory protection that certain respirator is expected to provide to workers. the apf for paprs vary from 25 to 1000 depending on the type of facepiece selected (half mask, full facepiece, helmet/ hood, or loose-fitting facepiece), while apf of loose-fitting paprs is 25 [8] . the fit factor (ff) representing the concentration ratio in and out of the respirator was must exceed the apf by at least ten times in order for the fit to be deemed adequate [8, 12] . therefore, the loose-fitting paprs were assumed to have a protective effect when the ff ≥ 250. we measured the concentrations of ambient aerosol and particles inside the loose-fitting papr's hood during chest compression, and this ratio was set as the simulated workplace protecting factor (swpf). we used a tsi model 8026 particle generator (tsi inc., shoreview, mn) to generate sodium chloride aerosol and the portacount pro+8038 respirator fit tester (tsi inc., shoreview, mn) was used to measure the swpf in this simulation. we placed the ambient tube outside of hood, and the inlet of the respirator tube was placed at the midpoint between the participant's mouth and bottom of the nose. in realtime mode, swpf was continuously recorded every second. the participants performed continuous chest compressions without ventilation on the manikin in 2-min sessions, with 4-min rest between the sessions, while measuring swpf in real time (fig. 3) . the participants either used footrests or knelt on the bed on the right side of the manikin depending on their preference. participants wore papr until the end of the simulation and were not allowed to touch or manipulate the papr. participants were asked to inform the investigator when they felt that there was no air flow in the hood or the connection tube was dislodged. all cpr quality data were collected using a laerdal pc skill reporting system (laerdal medical). to control the high cpr quality according to the aha guidelines, one investigator watched a computer monitor and provided feedback to each participant in real time [13] . the survey had 9 questions about papr use by a 5-point likert scale. after completing the simulation, participants were asked about the degree of comfortability to don or doff, difficulty to breathe through the papr, obstruction of vision, interrupting communication, skin irritation, and interference with ability. the investigators asked the participants three questions to assess the difficulty in communication during the 2-min operation time. the investigators gave feedback to the participants in real time to maintain the participants' cpr quality during the chest compressions. based on the above, the participants subjectively assessed the difficulty in communication or listening after the simulation. the primary outcome was any failure of protection (swpf b250) during three sessions of chest compression. the secondary outcome was device problem including tube disconnection or mechanical failures during the simulation and level of user experience of the participants. a sample size calculation was made in terms of primary outcome achievement. to achieve a ratio of the fit factor of papr n250 of 99% in 95% confidence interval within ±5% by clopper-pearson's interval, 91 participants were required [14] . standard descriptive statistics were used to present all data. categorical variables are presented as number with percentages. continuous variables are given as medians with interquartile ranges (iqrs). we estimated the smoothing graph for each individual swpf and the mean swpf during chest compression for each overall, 91 participants completed the simulation. table 1 presents the demographic characteristics of the study participants. sixty-seven (74%) of the participants were female, and the median age was 29 (iqr: 26-32) years. occupations of participants were medical doctors (n = 41; 45%), nurses (n = 44; 49%), and emergency medical technician (n = 6; 6%). most participants were certified as acls or bls providers (n = 76; 83%) by aha, and 79% of the participants had a normal body mass index. during the simulation, the quality of the chest compression including rate, depth, recoil, and correct hand position met the criteria of high quality cpr according to the 2015 aha guidelines. the primary outcomes are shown in table 2 and fig. 4 . none of the participants had their swpf below 250 during three sessions of chest compression. the median value (iqr) of swpf was 17,063 (10,145-26,373) in the first session, 15,683 (9477-32,394) in the second session, and 16,960 (7695-27,279) in the third session. swpf changes over time using the locally estimated scatterplot smoothing (loess) method did not show any particular pattern for the first, second and third swpf during chest compression (fig. 4) . two cases of flow test failure and one case of tube disconnection occurred during the preparation and 2-min operation time; therefore, the investigators changed the equipment or adjusted the connection of the tube. however, there were no tube disconnections or machine failures during the chest compressions. the survey of user experience on the loose-fitting papr is shown in table 3 . most participants responded that the loose-fitting papr was comfortable to don (86%) and to doff (89%). the majority of participants rarely or never experienced difficulty breathing through the papr (93%) and did not experience fear or anxiety (90%). seventy-six (83%) respondents reported that they had little or no difficulty in verbally communicating but 22 (24%) answered that they had difficulty in listening when wearing papr. for the questionnaire about whether papr interfered with the ability to do chest compression, 74 (81%) stated rarely or never had such an experience. none of the participants dropped their swpf below 250 within total of 360 s during three sessions of chest compression in the simulation. furthermore, during the three sessions of chest compressions, the median swpf values of loose-fitting papr was over 15,000. a previous simulation study showed that the n95 respirator failed to provide sufficient protection, with the fit factor falling below 100 in 73% of participants during chest compressions [7] . this study demonstrates the safety of respiratory protection when the loose-fitting papr is used in chest compressions, thereby showing significant implications for the safety of hcws and the reduction of risks of transmission of respiratory pathogens. while several studies have evaluated the performance of the n95 respirators [7, 15, 16] , only a few investigations have addressed the protection offered by the paprs. gao et al. [12] evaluated the protection level of improperly sized loose-fitting papr using a manikin. the manikin fit factor values of the stretched-out and improperly sized loosefitting facepieces were significantly lower than those obtained for the undamaged facepieces; thus, the former is unlikely to provide an acceptable level of protection. they suggest that loose-fitting facepieces are properly sized to employees and remove stretched-out facepieces from the workplace. in the study of cohen et al. [17] , they obtained swpfs for five papr models representing different brands and facepiece styles. these respirators were tested on 12 volunteers performing 12 exercises to simulate real workplace activities. the swpf range for the loose-fitting hooded paprs was 240 to n250,000, suggesting a high degree of protection as well as a large variance among the swpfs. however, these activities did not include chest compressions, and our study examined for the first time the stability of loose-fitting papr in chest compressions. a study reported the case of a hcw being infected after pathogen exposure due to disconnection of the circuit of papr during the outbreak of mers-cov in 2015 [18] . since paprs are battery-operated to filter out contaminated air, malfunctioning machine, e.g., the disconnection circuit, battery discharge, and problems with the filter can be fatal. in this study, there were no cases of disconnections or mechanical failures during chest compression. however, during the preparation and 2 min operation time, there were three cases that failed the flow test or had a disconnected circuit, so the investigator adjusted connection of tube or changed the equipment. this suggests that it is important to perform flow testing and to check the operation during the preparation process. in addition, hcws need to be trained regularly to use papr well in clinical setting and provided the proper instructions to become familiar to use. loose-fitting paprs utilize a motorized fan to draw air through the respirator's air purifying elements, delivering clean air to the wearer through a facepiece that does not form an airtight seal with the wearer's face. there is a concern about potential risk of wearer exposure to contaminants if the breathing rate of the wearer exceeds the air flow rate supplied by the papr fan [9, 12] . in such an instance, ambient air could bypass the filters and enter the mask potentially exposing the wearer to contamination. moreover, chest compressions are dynamic and fast that the inhalation flow during higher work rates could exceed the air flow supplied by the papr. mackey et al. [19] measured overbreathing in one type of loose-fitting papr. their measurements showed that even when peak inspiratory flow rate exceeded the blower flow rate, the concentration of aerosol within the papr remained below 0.1% of the ambient concentration. thus, they assumed that the hood contributed a large dead volume that acted as a buffer against inward leakage of ambient aerosol. in this study, none of the participants dropped their swpf below 250 within total 360 s. however, one participant showed fluctuations in swpf values from 1442 to 2,883,675 at the first chest compression. therefore, during chest compression, increasing the flow rate of the loose-fitting papr could help maintain positive pressure. however, the further studies of different blower flow rates are needed to better understand the effect of the over breathing. in previous studies, loose-fitting paprs were considered more comfortable than n95 respirator because they reduce breathing effort and temperature with cool airflow and do not require a fit test, as well as have wide protection through the head, hair, eye, and neck [20, 21] . however, it has been a concern that overall protective facemasks as loose-fitting paprs could impair communication [22] . in our survey, most of the participants (83%) responded that they rarely or never experienced difficulty in verbal communication. besides the protective effect, the convenience of papr is important because it affects work performance. in this study, most participants (81%) did not think that the loose-fitting papr interfered with the ability to perform chest compression. therefore, the findings of this study support the safety and convenience of the loose-fitting papr during chest compressions. however, 22 (24%) of participants responded that they had difficulties listening "most of the time or always". in actual clinical situations that require more communication and various roles, these difficulties could be greater. therefore, training for hcws and further research are needed to facilitate communication and work performance when wearing paprs. first, although we performed this study in actual ed settings to reflect real-life clinical situations, simulation environments have inherent limitations. performing chest compressions on a manikin lacks patient interaction. in addition, the participants only performed continuous chest compressions without ventilations. cpr is a complex intervention in the clinical setting. several tasks are performed by hcws in an uncontrolled and confusing environment. interactions with other hcws during chest compressions in a realistic situation may affect outcomes including device problems (i.e., tube disconnection or mechanical failures) and difficulties in communication. second, we evaluated only one papr model and one-sized loose-fitting hood manufactured by one company. in particular, there was no consideration of each participant's face size. therefore, there is a limit to generalizability of our results to other models. third, we did not consider the infections associated with donning and doffing of papr and disinfection of equipment. forth, we performed a flow test before the simulation, but the blower flow rate in hood was not measured in real time. moreover, the filtration efficiency of paprs filter was not evaluated in this study. finally, cpr quality may be affected by the use of paprs. however, our study aimed to assess the effect of paprs on respiratory protection during chest compressions and not on the quality of the chest compressions. therefore, we provided feedback to each participant in real time to ensure high cpr quality to reflect real-world situations. further studies are needed to determine the impact of papr use on the quality of chest compressions. in conclusion, the loose-fitting paprs provided sufficient respiratory protection and comfort during chest compression. further studies are needed to provide generalized guidance on the level of respiratory protection during cpr for patients with airborne diseases using several types of paprs in different cpr activities. funding sources infection prevention and control of epidemicand pandemic-prone acute respiratory infections in health care. world health organization personal protective equipment and improving compliance among healthcare workers in high-risk settings infection prevention for the emergency department: out of reach or standard of care mers-cov outbreak following a single patient exposure in an emergency room in south korea: an epidemiological outbreak study middle east respiratory syndrome coronavirus in the last two years: health care workers still at risk sars transmission among hospital workers in hong kong n95 filtering facepiece respirators do not reliably afford respiratory protection during chest compression: a simulation study authored by the division of occupational health and safety (dohs) respiratory protection program (rpp) manager development of a manikin-based performance evaluation method for loose-fitting powered air-purifying respirators the use and effectiveness of powered air purifying respirators in health care: workshop summary middle east respiratory syndrome (mers) guideline 2019 performance of an improperly sized and stretched-out loose-fitting powered air-purifying respirator: manikin-based study american heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care myunghee cho paik. statistical methods for rates and proportions, third edition physiological impact of the n95 filtering facepiece respirator on healthcare workers assessing real-time performances of n95 respirators for health care workers by simulated workplace protection factors simulated workplace protection factor study of powered air-purifying and supplied air respirators seroprevalence of middle east respiratory syndrome coronavirus among healthcare personnel caring for patients with middle east respiratory syndrome in south korea over breathing a loose-fitting papr health care workers' views about respirator use and features that should be included in the next generation of respirators powered air-purifying respirator use in healthcare: effects on thermal sensations and comfort analysis of user preference with n95 and powered air-purifying respirators in a healthcare work environment this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. the authors have no potential conflicts of interest to declare. key: cord-349909-hmyv1nep authors: misa, nana-yaa; perez, berenice; basham, kellie; fisher-hobson, essence; butler, brittany; king, kolette; white, douglas a.e.; anderson, erik s. title: racial/ethnic disparities in covid-19 disease burden & mortality among emergency department patients in a safety net health system date: 2020-09-24 journal: am j emerg med doi: 10.1016/j.ajem.2020.09.053 sha: doc_id: 349909 cord_uid: hmyv1nep background: we sought to examine racial and ethnic disparities in test positivity rate and mortality among emergency department (ed) patients tested for covid-19 within an integrated public health system in northern california. methods: in this retrospective study we analyzed data from patients seen at three eds and tested for covid-19 between april 6 through may 4, 2020. the primary outcome was the test positivity rate by race and ethnicity, and the secondary outcome was 30 day in-hospital mortality. we used multivariable logistic regression to examine associations with covid-19 test positivity. results: there were 526 patients tested for covid-19, of whom 95 (18.1%) tested positive. the mean age of patients tested was 54.2 years, 54.7% were male, and 76.1% had at least one medical comorbidity. black patients accounted for 40.7% of those tested but 16.8% of the positive tests, and latinx patients accounted for 26.4% of those tested but 58.9% of the positive tests. the test positivity rate among latinx patients was 40.3% (56/139) compared with 10.1% (39/387) among non-latinx patients (p < 0.001). latinx ethnicity was associated with covid-19 test positivity (adjusted odds ratio 9.6, 95% confidence interval: 3.5–26.0). mortality among black patients was higher than non-black patients (18.7% vs 1.3%, p < 0.001). conclusion: we report a significant disparity in covid-19 adjusted test positivity rate and crude mortality rate among latinx and black patients, respectively. results from ed-based testing can identify racial and ethnic disparities in covid-19 testing, test positivity rates, and mortality associated with covid-19 infection and can be used by health departments to inform policy. in late december 2019 a novel coronavirus infection (covid-19, sars-cov2) emerged from wuhan, china and quickly became a pandemic with unprecedented impact on worldwide health care systems, social practices, and economies. 1 by september 2020, covid-19 infected over 28 million people and resulted in nearly 900,000 deaths across 188 countries. the first known case in the united states (us) occurred in january 2020 and there are now more than 6.4 million cases and over 191,000 deaths nationally. [1] [2] [3] early data from china and europe suggest people with older age, hypertension, diabetes, and obesity are at increased risk of having a more serious illness course and death. 4, 5 while us data reflects a similar pattern of disease severity and mortality among older patients with pre-existing medical conditions, several reports also highlight a disproportionate burden of covid-19 infection and related morbidity and mortality among racial and ethnic minorities. 6 as of june 2020, black and latinx people accounted for 22% and 33% of total covid-19 cases in the us but make up only 13% and 16% of the total us population, respectively. 7 in addition limited preliminary data shows latinx communities have a higher daily positivity rate in certain parts of northeastern us including baltimore, maryland. 8 in new york city, the initial us epicenter of the pandemic, latinx patients constituted 29% of the population but mortality was 34% with similar disparities amongst blacks who made up 24% of the population but 28% of the mortality. 9 blacks have also been shown to have higher rates of hospitalization for covid-19 than all other groups, and have higher mortality rates than whites. 10 these statistics from national data are reflected in local communities within california. at the end of april 2020, the university of california, san francisco performed covid-19 tests on nearly 3,000 residents and workers in the highly diverse mission district of san francisco and reported a 2.1% test positivity rate. despite making up only 44% of those tested, latinx patients accounted for 95% of those testing positive. this report also suggests that people who had lower annual income levels, greater household sizes and were unable to work from home, were more likely to test positive for covid-19. 11, 12 nonetheless overall disease prevalence is still likely underestimated in black and latinx communities due to notably poor access to testing for these populations. 6 differences in covid-19 health outcomes have been attributable to underlying racial and ethnic health disparities rooted in systemic racism and marginalization. these disparities have resulted in social and economic inequality including limited access to housing, healthy food options, healthcare facilities and health insurance. language barriers and epigenetic health effects of racial bias have also been cited as major contributors. [13] [14] [15] [16] [17] [18] [19] blacks have a higher rate of chronic health conditions at a younger age compared to the general population and have the highest rates of death from heart disease, cerebrovascular disease, cancer and hiv/aids compared to all other racial and ethnic groups in the us. latinx americans are almost twice as likely as their non-latinx counterparts to die from diabetes. 19, 20 these health disparities have been associated with increased risk of severe illness from covid-19 infection. 21 j o u r n a l p r e -p r o o f journal pre-proof importance as a safety net provider, eds provide care to medically and socially vulnerable populations. data has shown that significant number of symptomatic patients present to eds for influenza-like illness (ili) and testing for covid-19. 22 safety net eds have an important role in evaluating racial and ethnic minorities with ili who have inequitable access to covid-19 testing. 23 to our knowledge there is no existing literature on the racial and ethnic disparities in covid-19 positivity among symptomatic patients tested for covid-19 in the ed setting. results from ed-based testing can identify racial and ethnic disparities in covid-19 testing, test positivity rates, and morbidity and mortality that can be used by public health departments to inform policy and distribution of resources. we aim to examine racial and ethnic disparities in covid-19 disease burden among patients tested in three eds that are part of an integrated public healthcare system. we use multivariable logistic regression analysis to assess for demographic and clinical factors associated with covid-19 test positivity, and we examine the 30-day in hospital mortality among patients admitted with covid-19. this is a retrospective cohort study of patients tested for covid-19 at three eds within the alameda health system (ahs) between april 6 to may 4, 2020. april 6 was chosen as the study start date because this is the date when covid-19 testing first became available for ed patients at ahs. prior to this time, only patients admitted to the hospital were eligible for covid-19 testing. this study was approved by the ahs institutional review board with a waiver of written informed consent as the study posed no more than minimal risk to patients. we adhered to strobe guidelines for conducting observational studies in epidemiology. the primary outcome was covid-19 test positivity rate stratified by race and ethnicity, and the secondary outcome was 30-day in hospital mortality. we also report descriptive data on the epidemiology of covid-19 among patients presenting to ahs eds. alameda health system is an integrated public health system with three medical eds that geographically span alameda county, california: 1) highland hospital is an urban teaching hospital in oakland, with an accredited 4year emergency medicine residency program, and an annual volume of 65,000 patients per year; 2) san leandro during the study period, guidelines for testing were issued by the ahs covid-19 testing committee, a multidisciplinary working group of physicians from infectious disease, laboratory, emergency and internal medicine. due to a limited supply of covid-19 tests, testing was restricted to the ed, the highland urgent care clinic, and the inpatient medicine service. test eligibility criteria were agreed upon and distributed across the medical system. eligible patients included: 1) those admitted to the medicine service for presumed covid-19 infection; 2) ed patients with a clinical syndrome consistent with covid-19 infection, who did not require hospitalization, but determined by the treating physician to be of moderate to high risk for a severe illness course due to medical comorbidities such as diabetes, heart disease, pulmonary disease, or kidney disease; or any patient felt to be infected with covid-19 with who had social factors impacting disease transmission and community spread, such as being homeless or congregate living. ahs is unable to accommodate direct inpatient admissions from the community or from other facilities; therefore, all patients admitted for covid-19 were admitted through the ed. covid-19 testing was performed using pcr assays and conducted at either the alameda county department of public health laboratory or the university of california san francisco laboratory. all unique ed patients tested for covid-19 were eligible for inclusion. we excluded tests performed during inpatient admission, as part of disease monitoring or assessment for viral clearance, and those performed in the urgent care. only the index ed covid-19 test was included in the analysis for patients who had multiple tests. race and ethnicity was self-identified by patients during ed registration from fixed categories. we analyzed data from the electronic health record (ehr) and stored it in redcap (a secure online data collection instrument). redcap was used by the ahs ed covid-19 public health team for follow-up and surveillance protocols. all patients who were tested for covid-19 at an ahs ed were included in this dataset. patients who tested positive for covid-19 had past medical and social history documented in the dataset prospectively, and study investigators conducted a retrospective chart review for patients who tested negative for covid-19. the past medical and social history in the redcap data collection instrument included co-morbidities, social/epidemiological factors (homelessness, group living, behavioral health concerns), race, ethnicity, age, and primary care physicians (pcp) information. we conducted a final review of admitted patients on f 4, 2020 to assess for 30-day in hospital mortality. descriptive analyses were performed for all variables. categorical data are reported as numbers and percentages and continuous data are reported as means with standard deviation (sd). bivariate statistical tests, including the wilcoxon rank sum test, the chi-square tests, or fisher's exact test, were used to compare variables. we conducted a power analysis for the regression model to ensure adequate power of 0.8 as convention to detect a 6% difference in test positivity between racial and ethnic groups. to adequately power the study, we found we needed 457 unique j o u r n a l p r e -p r o o f journal pre-proof patient encounters. we pre-specified the regression model to contain covid-19 positivity as the dependent variable, with the following predictor variables: race and ethnicity; age; medical co-morbidities (that may influence disease severity); documented epidemiologic concern (defined as healthcare worker or living with elderly family members); skilled nursing facility residence; whether or not a patient had a pcp (to control for access to medical care); and which ahs ed conducted the test to control for geographic and hospital site clustering. all analysis was performed in stata version 13.1 (statacorp, college station, tx). there were 526 patients tested for covid-19 in the ahs eds from april 6 through may 4, 2020, of whom 95 (18.1%) tested positive. demographics of patients tested for covid-19 from the overall cohort, as well as from each ed, can be found in table 1 table 3 shows the rates of hospital admission and in-hospital mortality for patients who tested positive for covid19 . of the 95 patients with covid-19, 52 (54.7%) were admitted (17 required icu care), 4 (4.2%) died, and 2 (2.1%) were still in the hospital as of june 4 th 2020. of the two patients remaining in the hospital, 1 was white and 1 was latinx. the mean age of patients admitted to the icu was 63.7 (sd 14.6) and the mean age of the patients who died was 82.5 (sd 8.4); all 4 patients who died lived in a skilled nursing facility and had >3 chronic medical conditions. crude mortality among black patients was significantly higher than non-black patients (18.7% vs 1.3%, p<0.01) our study reports the outcomes of ed-based covid-19 testing within a single health care system in northern california and may not be generalizable to other care settings. importantly, covid-19 testing was driven by an institutionally defined policy, determined by local expert consensus to test vulnerable populations with severe symptoms, and influenced, in part, by test availability. our data does not report the prevalence of covid-19 within our ed population, but rather the positivity rate among a selected group of symptomatic and vulnerable patients. our data does not allow for the comparison of patients with cough, fever, or ili who may have met our eligibility criteria for covid-19 testing, but who were not tested. during the time-period of this study we did not have a diagnosis code for suspected covid-19 and our ehr screening tool was based on travel history and not symptoms. how the role of race, ethnicity, and other factors, such as language barriers, bias covid-19 testing requires further study. lastly, given the small numbers of deaths in our study population using a 30-day inpatient mortality outcome, we were unable to control for factors associated with mortality, such as medical comorbidities, race/ethnicity, or socioeconomic variables. among patients tested across three urban eds in an integrated public health system in northern california, we found significantly higher covid-19 positivity in the latinx community. while ed testing within an integrated area and california. 10 one definition of a healthcare disparity is defined as a difference in outcome by race or ethnicity not attributable to access to care. 23 a strength of our study is that we demonstrate the disparity in covid-19 test positivity rate to be significant even after controlling for access to care, age, medical co-morbidities, social factors and site of testing. this analysis helps frame the discussion around healthcare disparities and can focus responses tailored to specific communities. the higher rate of positivity in latinx patients may be explained by socioeconomic factors that put these communities at greater risk for exposure to infection. of the nearly 3,000 people tested for covid-19 in the san francisco mission study, 62 were positive, 95% of whom were latinx. of the 62 patients who tested positive for covid-19 in this study, 90% stated they were unable to work from home, 89.9% reported a household income of <$50,000 per year, 59.6% report a total household size of 3-5 people and 28.8% of >5 people. [11] [12] these factors may hold true in our population as well, although we did not examine the contribution of socioeconomic status and covid-19 test positivity in our study. racial and ethnic minorities are more likely to live in densely populated areas, in multi-generational group homes, and have a higher representation in jails, prisons and detention centers. 25 in addition, many racial and ethnic minorities are more likely to work as essential workers in the service industry. these include positions in agriculture, in meat packing plants, as day laborers, and as caretakers where maintaining social distancing is difficult. one such example is the recent outbreak of covid-19 in workers in the meat-packing industry, most of whom are latinx, that was significant enough to cause a national decrease in the us meat supply. 26, 27 moreover, latinx have the lowest rates of paid sick leave and may not be financially able to take time off work when they or a family member gets sick with covid-19. 28 in our study, we found that the median age of latinx patients who tested positive for covid-19 to be nearly 20 years younger than non-latinx patients, suggesting that this community may be more likely to be working and unable to shelter in place at home due to financial obligations. within ahs, highland and san leandro hospitals had higher test positivity rates of covid-19 (19.8% and 24.4% respectively) compared to alameda hospital (2.6%), which cares for a slightly less diverse patient population with a higher proportion of patients that have private insurance. these findings highlight the unequal impact on hospitals caring for vulnerable populations and the disparate impact of covid-19 geographically, even within integrated health systems. while our sample size is relatively small, we did find a higher unadjusted mortality rate among black patients. this disparity is consistent with other published data from the covid-19 pandemic [6] [7] [8] [9] . however, it is difficult to interpret due to the small overall number of deaths at ahs during this time period. a recent study of 3,626 patients in a large cohort in louisiana revealed that 70.6% of patients hospitalized for covid-19 who died were black even though they comprised only 31% of the population. 29 our findings suggest that future work should not only take into account disparities in disease burden within a health system, but also disparities in mortality within each community. despite the higher test positivity rate among latinx patients, the relatively lower mortality and icu admission rates j o u r n a l p r e -p r o o f journal pre-proof may be age related. among our cohort, latinx patients diagnosed with covid-19 were significantly younger than non-latinx patients. these findings highlight the need for focused interventions that target both the black and latinx communities. emergency departments have a history of engaging in public health and epidemiology, shaping screening recommendations and detecting outbreaks for influenza, hiv, and hepatitis c virus infections. [31] [32] [33] a similar approach should be implemented among eds during the covid-19 pandemic. as part of the public health programs, eds can monitor for outbreaks and disparities in disease burden as well as implement targeted and culturally appropriate contact tracing. the data collected as part of ed surveillance has helped to inform public health policies: including prioritizing stand-up testing sites in neighborhoods with high proportions of latinx citizens and identifying the need for isolation housing for patients living in households with high numbers of people. in the time since this study period ended, the ed public health team contributed data to the county identifying an emerging outbreak among mexican and guatemalan communities who primarily speak mayan indigenous languages, and the ahs ed public health team became a part of the newly formed alameda county covid-19 latinx task force. while community testing sites have increased significantly since the onset of the pandemic, eds will remain highvolume testing locations for covid-19 for the most symptomatic patients, as well as patients coming from disadvantaged communities. safety-net eds may be more sensitive to the early detection of outbreaks in vulnerable populations, including immigrant communities, patients experiencing homelessness, as well as those with significant psychiatric and substance use disorders. close attention to these communities is critical to covid-19 public health responses, and eds should leverage any existing public health infrastructure for these purposes. for example, staff from the ahs hiv and hepatitis c virus screening program were re-tailored to facilitate covid-19 follow up, wellness checks, and care coordination with primary care and the public health department using pre-existing relationships and workflows. additional ahs emergency medicine public health collaborations have included standup community testing sites under the direction of an em physician working with the county public health department for neighborhoods disproportionately impacted by covid-19, while another em physician has spearheaded efforts to house patients experiencing homelessness affected by covid-19. 34, 35 lastly, as the covid-19 pandemic ebbs and flows, there will be an increased role for ed testing of both symptomatic and asymptomatic patients. close coordination with public health departments and contact tracing programs will be critical to sustaining low rates of transmission within communities. among three eds in an integrated public health system, we report a significant disparity in covid-19 disease burden in the latinx community, and disproportionate mortality among black patients. these findings are consistent with other regional and national data and suggest that where racial and ethnic minorities live and work contributes to a greater risk of infection with covid-19. these communities are often less able to shelter in place, work from ethnicity is non-latinx unless specified. epidemiologic concern (as documented in the medical record) defined by: living with family member over 60 years old, lives with family members with chronic diseases (diabetes, lung disease, heart disease), healthcare workers, other essential service worker. medical co-morbidity (as documented in the medical record) defined by: diabetes, hypertension, chronic or end stage kidney disease, human immunodeficiency virus, chronic obstructive pulmonary disease or asthma, active cancer, history of stroke, or current smoker. a novel coronavirus from patients with pneumonia in china coronavirus covid-19 global cases. the center for systems science and engineering first case of 2019 novel coronavirus in the united states clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study. the lancet diabetes mellitus is associated with increased mortality and severity of disease in covid-19 pneumonia -a systematic review, meta-analysis, and meta-regression covid-19: testing inequality in new york city black-white risk differentials in covid-19 (sars-cov2) transmission, mortality and case fatality in the united states: translational epidemiologic perspective and challenges sars-cov-2 positivity rate for latinos in the hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 -covid-net, 14 states initial results of mission district covid-19 testing announced. initial results of mission district covid-19 testing announced | uc san francisco mission district (the mission association of simulated patient race/ethnicity with scheduling of primary care appointments the aca's impact on racial and ethnic disparities in health insurance coverage and access to care racial/ethnic and gender disparities in health care use and access language barriers, physician-patient language concordance, and glycemic control among insured latinos with diabetes: the diabetes study of northern california (distance) providing high-quality care for limited english proficient patients: the importance of language concordance and interpreter use understanding how discrimination can affect health r e -p r o o f journal pre-proof risk-for-health-and-economic-challenges-due-to-covid-19 unequal treatment. institute of medicine: national center for biotechnology information cardiovascular complications in covid-19 emergency department visits percentage of visits for covid-19-like illness (cli) or influenza-like illness (ili) covid-19: testing inequality in new york city. nber working papers covid-19 and african americans covid-19 in racial and ethnic minority groups.‖ centers for disease control and prevention covid-19 among workers in meat and poultry processing facilities -19 states eeo-1 aggregate report for meat packing plants. u.s. equal employment opportunity commission racial and ethnic disparities in access to and use of paid family and medical leave: evidence from four nationally representative datasets hospitalization and mortality among black patients and white patients with covid-19 covid-19 deaths analyzed by race and ethnicity google flu trends: correlation with emergency department influenza rates and crowding metrics rapid hiv testing in emergency departments--three high prevalence of hepatitis c infection among adult patients at four urban emergency departments coronavirus test sites are opening in east oakland's most impacted neighborhoods 2 patients remain admitted as of 6/4/2020. intensive care admission and mortality rates are based on the row variable as the denominator. *ethnicity non-hispanic/latino unless specified. **many patients had more than one comorbidity.j o u r n a l p r e -p r o o f journal pre-proof key: cord-268049-7xqln70d authors: montrief, tim; ramzy, mark; long, brit; gottlieb, michael; hercz, dan title: covid-19 respiratory support in the emergency department setting date: 2020-08-08 journal: am j emerg med doi: 10.1016/j.ajem.2020.08.001 sha: doc_id: 268049 cord_uid: 7xqln70d introduction: severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2), which causes the coronavirus disease 2019 (covid-19), may result in severe complications, multiorgan dysfunction, acute respiratory failure, and death. sars-cov-2 is highly contagious and places healthcare workers at significant risk, especially during aerosol-generating procedures, including airway management. objective: this narrative review outlines the underlying respiratory pathophysiology of patients with covid-19 and discusses approaches to airway management in the emergency department (ed) based on current literature. discussion: patients presenting with sars-cov-2 infection are at high risk for acute respiratory failure requiring airway management. among hospitalized patients, 10–20% require intensive care unit admission, and 3–10% require intubation and mechanical ventilation. while providing respiratory support for these patients, proper infection control measures, including adherence to personal protective equipment policies, are necessary to prevent nosocomial transmission to healthcare workers. a structured approach to respiratory failure in these patients includes the use of exogenous oxygen via nasal cannula or non-rebreather, as well as titrated high-flow nasal cannula and non-invasive ventilation. this review offers several guiding principles and resources designed to be adapted in conjunction with local workplace policies for patients requiring endotracheal intubation. conclusions: while the fundamental principles of acute respiratory failure management are similar between covid-19 and non-covid-19 patients, there are some notable differences, including a focus on provider safety. this review provides an approach to airway management and respiratory support in the patient with covid-19. coronavirus disease 2019 (covid-19) caused by severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) has become a pandemic involving millions of people and causing hundreds of thousands deaths worldwide. 1 covid-19 was first reported within wuhan, china in december 2019 and has spread rapidly. 2 patients presenting with covid-19 are at high risk for acute respiratory failure necessitating advanced airway management. [2] [3] [4] overall, the presence of hypoxic respiratory failure among covid-19 patients approaches 20%. [5] [6] [7] data from china reported that up to 41% of all patients with covid-19 required oxygen therapy, 4% to 13% required noninvasive ventilation (niv), and 2.3% to 12% required intubation and mechanical ventilation. 3, 5 risk factors for developing acute respiratory failure appear to include male gender; age over 60 years; and comorbidities including diabetes, active cancer, and immunocompromising states. 5, [8] [9] [10] healthcare workers (hcws) caring for this population are at high risk of contracting sars-cov-2 via large droplets, respiratory secretions, and contact with contaminated surfaces. 11 airway management is particularly high risk because it involves aerosol-generating procedures. 11, 12 emergency providers must be prepared to manage patients with acute respiratory failure due to sars-cov-2. in this review, we provide an overview of the underlying respiratory pathophysiology of sars-cov-2, followed by an approach to airway management for suspected or healthcare workers should follow the infection control policies at their individual healthcare institutions. many guidelines recommend exogenous oxygen administration as an initial therapy in patients with mild hypoxemic respiratory failure due to covid-19. [15] [16] [17] supplemental oxygen is recommended if the patient"s oxygen saturation (spo 2 ) is less than 90%, with a target spo 2 of no higher than 96%, based on recommendations from several societies, including the society of critical care medicine (sccm). 14, 18 clinicians should assess patient respiratory status inclusive of mental status and respiratory effort (e.g., work of breathing, respiratory rate) rather than oxygen saturation alone, when determining the need for airway intervention. in patients with mild hypoxemia due to sars-cov-2 but no evidence of respiratory failure requiring immediate endotracheal intubation, supplemental oxygen may be provided. 4 a strategy of oxygen escalation therapy may assist patients, in which nasal cannula (nc) can be started at 6 l/min. 19 if the patient does not improve with nc, further steps include venturi mask up to 50% or non-rebreather mask up to 15 l/min, non-rebreather at 15 l/min in addition to nc at 6 l/min, high flow nasal cannula (hfnc), and then niv (figure 1 ). 20 oxygen flow of 6 l/min or greater is considered high-flow oxygen and may cause aerosolization of viral pathogens, although this is controversial. [21] [22] [23] respiratory support of patients with sars-cov-2 requires modification in order to minimize viral spread. for instance, a standard surgical mask should be worn over the nc, non-rebreather, or j o u r n a l p r e -p r o o f venturi mask to reduce the risk of droplet spread. 4 for patients requiring higher oxygen delivery via the use of a simple facemask or nonrebreather, an exhalation filter can be attached; however, this strategy has not been thoroughly evaluated in terms of viral transmission. 4 as a result they are not recommended for routine use in patients with sars-cov-2 respiratory disease. 20 when necessary, non-rebreather masks are preferred over simple facemasks. 19 similarly, nebulization of medications via simple facemask should be avoided in this population. 4, 18, 19 bronchodilators may be administered by metered-dose inhalers if necessary. 4 hfnc has become more prevalent in the years after the sars outbreak and has been found to decrease the need for mechanical ventilation in patients with acute hypoxemic respiratory failure and potentially improve 90-day mortality. [24] [25] [26] hfnc is an emerging support modality for patients with covid-19 and has been associated with increased survival in covid-19 patients when compared to either niv or invasive mechanical ventilation. 9, 27, 28 while the risk of bacterial transmission with hfnc is low, the risk of respiratory viral pathogen transmission remains unclear. [29] [30] [31] [32] based on currently available evidence, the who states that "hfnc and niv systems with good interface fitting do not create widespread dispersion of exhaled air and therefore should be associated with [a] low risk of airborne transmission." 15 the risk of respiratory pathogen transmission when using hfnc is subject to a variety of factors, including the duration of support, maximal flow rate, patient sneezing or coughing, cannula fit, and patient cooperation. 20 special attention must be paid to the connections between the oxygen tubing and the nasal cannula. 19 any disruption to this connection may lead to dispersal of sars-cov-2. 33 some experts have recommended placement of a surgical mask over the hfnc to reduce viral transmission. 19, 34 patients on hfnc should be placed under airborne precautions in a negative-pressure room, if available. 15, 19 j o u r n a l p r e -p r o o f hfnc provides gas flows between 40-60 l/min and may not result in aerosolization when compared to a patient on standard nasal cannula. 35 many guidelines, including those by australian and new zealand intensive care society (anzics), the who, and the surviving sepsis campaign recommend the use of hfnc in covid-19 patients presenting with acute hypoxemic respiratory failure unresponsive to conventional oxygen therapy. 15, 16, 18 several groups have developed management strategies utilizing hfnc preferentially over niv. 9, 36 it is prudent to avoid hfnc in patients presenting with severe respiratory distress or failure, thoracoabdominal asynchrony, increasing vasopressor support, refractory hypoxemia despite other therapies, or a "clinical trajectory that suggests mechanical ventilation is inevitable". 4,25,37 niv may be more effective for other forms of respiratory failure, such as hypercapnic respiratory failure or obstructive airway disease. 18 however, hfnc can increase airway pressures, improve oxygenation, reduce dead space, and reduce a patient"s work of breathing and can be utilized in patients with covid-19. 38 international guidelines on the use of niv for covid-19 patients vary, with many guidelines recommending against the routine use of niv due to increased risk of virus aerosolization and unproven utility in patients with ards. 20 notably, the sccm guidelines on the management of critically ill patients with covid-19 recommend "a trial of niv with close monitoring and shortinterval assessment for worsening of respiratory failure" if hfnc is not available and there is no urgent indication for intubation. 18 current epidemiological forecasts suggest that the requirements for mechanical ventilation may outpace the current ventilator capacity of many hospitals if niv is not routinely used. 18 niv does have limitations. in previous cohorts of patients with acute respiratory failure due to influenza a, niv failed in up to 85% of cases, portending a higher mortality compared to patients j o u r n a l p r e -p r o o f treated with invasive ventilation. 39, 40 in a group of 302 patients with middle east respiratory syndrome (mers) across 14 saudi arabian hospitals, 92% of patients trialed on niv failed to substantially improve, eventually requiring intubation. 41 a relatively similar failure rate was noted in a cohort of patients with covid-19 associated respiratory failure in china. 9 there is also concern that niv may worsen lung injury due to elevated transpulmonary pressures and large tidal volumes. 42, 43 niv use in patients with excessive respiratory efforts may induce substantial intrathoracic negative pressures and self-inflicted lung injury, worsening hypoxemia. 43 additionally, the use of niv may delay initiation of mechanical ventilation until the patient has no reserve, thereby increasing the risk of inappropriate donning of adequate ppe and transmission to hcws due to time pressures to establish a definitive airway. 4 although some centers reported successful management of sars patients with niv, there are documented cases of nosocomial transmission between patients in the same hospital. 44, 45 this risk of aerosolization and viral transmission is variable, depending on a variety of factors, including the support parameters, model of the machine, and mask type. 19, 46 this risk could be diminished by use of appropriate viral exhalation filters on the niv and cohorting high-risk patients in an appropriate airborne isolation room. 19 however, any significant mask leak may render filtration of viral pathogens incomplete. 4 despite these limitations, niv may improve patient respiratory status and is a component of current guidelines. 18, 19 niv should be used in patients with covid-19 with hypercarbic respiratory failure, refractory hypoxemia despite other therapies (including hfnc), or if hfnc is not available. 18 if utilized for patients with covid-19, special attention should be paid to the use of viral filters, closed circuit systems, adequate mask seal, use of helmet systems (if available), appropriate ppe use, and appropriate isolation in a negative pressure room. 19 when available, a helmet-based niv j o u r n a l p r e -p r o o f interface may have several advantages over traditional mask-based niv, including decreased risk of aspiration and environmental contamination. 33, 47 in one randomized clinical trial of 83 patients with ards, a niv helmet reduced intubation rates and 90-day mortality compared to traditional niv facemask. 48 many clinicians have recommended awake proning or repositioning of patients on supplemental oxygen, hfnc, and niv. prone positioning of the patient may improve respiratory status and oxygenation, decreasing the need for endotracheal intubation in early ards. 49, 50 while proning or repositioning may improve oxygenation, clinicians should be aware that this typically induces a temporary, non-sustainable improvement in oxygenation, and patients may require movement to another position (i.e., left lateral recumbent, right lateral recumbent, sitting upright) to maintain the benefit associated with this technique. 49 patient comfort is important during proning/repositioning, and maternity cushioning devices may be beneficial. regardless of oxygenation, these patients remain at risk for deterioration and must be monitored closely. there are currently no evidence-based guidelines describing when to pursue intubation and mechanical ventilation for patients with sars-cov-2. 19 however, in cases of severe respiratory distress or refractory hypoxemia despite oxygen escalation therapy including niv, the patient should undergo endotracheal intubation and invasive ventilation. 14 many patients who develop acute respiratory failure do so with hypoxemia and minimal signs of respiratory distress or tachypnea (so called "silent hypoxemia"), making work of breathing alone a potentially unreliable indicator for failure of niv. 51, 52 thus, clinicians should consider patient mental status, work of breathing, respiratory rate, and oxygen saturation in their decision to intubate. in a series of 202 j o u r n a l p r e -p r o o f journal pre-proof covid-19 patients undergoing tracheal intubation in two hospitals in wuhan, china, more than 75% of patients were hypoxemic (sao 2 <90%) before induction. 53 the authors hypothesized that the shortage of available hospital beds during the covid-19 pandemic, as well as result in delayed recognition respiratory failure severity due to "silent hypoxemia," may have led to delays in the decision to intubate. 53 the chinese society of anesthesiology task force on airway management recommends endotracheal intubation for patients showing no improvement in respiratory distress, tachypnea (respiratory rate >30 breaths per minute), and poor oxygenation (pao 2 to fio 2 ratio ≤150 mmhg) after a 2 hour trial of hfnc or niv. 8 however, these recommendations are expert consensus and lack robust supporting evidence. 54 some have liberalized their criteria, recommending that physicians consider intubation in any patient with respiratory distress (respiratory rate >30 breaths per minute) or spo 2 less than 93% on room air and a pao 2 to fio 2 ratio less than 300 mmhg. 54 we recommend using a combination of factors in deciding to intubate, including progressively increasing oxygenation requirements despite oxygen escalation therapy, increasing vasopressor support, persistent thoracoabdominal asynchrony, increasing work of breathing, increasing respiratory distress, low rox index (determined by oxygen saturation as measured by pulse oximetry divided by fraction of inspired oxygen [fio2] divided by respiratory rate), hypercarbia, and altered mentation. 19, 25, 36, 37, 55 however, this must be balanced with potential resource limitations (availability of ventilators or staff, intensive care unit capability), clinical trajectory, and individual patient wishes. 19 airway management for patients with suspected or confirmed covid-19 shares similarities with techniques in non-covid-19 patients, with some notable exceptions, including an emphasis on j o u r n a l p r e -p r o o f staff safety throughout the procedure. 56 the increased risk of transmission of viral pathogens to hcws with subsequent attempts necessitates the use of familiar and reliable airway techniques to ensure the greatest likelihood of first pass success. 23 airborne precautions are indicated during the peri-intubation period, as the highest viral load appears in airway secretions of patients with covid-19. 5,57 careful preparation and planning at the institutional level addressing appropriate equipment, staff preparedness, development of airway packs and endotracheal intubation checklists (table 1 and figure 2 ), and availability of ppe are essential. 23 this should be augmented and evaluated using frequent in-situ simulation. 23, 58 patient. endotracheal intubation is a high-risk procedure, with 10% of critically ill patients developing severe hypoxemia and 2% experiencing cardiac arrest. 59, 60 the first pass success rate for endotracheal intubation among critically ill patients is typically less than 80%, with a significant proportion requiring two or more attempts. 59 these figures are likely to be worse in the critically ill covid-19 patient due to the use of ppe and the patient"s physiological state. 23, 61 patients with covid-19 may experience myocardial injury which can worsen hemodynamic instability, lead to multiorgan failure, and reduce oxygen reserve. 62 moreover, fogging of eyewear when using ppe during intubation affects up to 80% of providers, which can make intubation attempts more challenging. 23 some clinicians have advocated for placement of a clear drape or box over the patients face to minimize aerosolization, but this may affect first pass success. 63 one study evaluating the use of aerosol boxes to protect hcw found reduced first pass success, longer time to intubation, and decreased laryngoscopic grade. 64 ppe may also decrease the clinician"s field of vision, lead to reductions in manual dexterity, and interfere with team communication. 65 institutions should create a mobile endotracheal intubation pack that is decontaminated after each use (table 1) . 23, 56 this pack should preferentially contain single-use equipment brought to the patient"s bedside during the procedure. 4,23 some institutions may choose to include appropriate ppe for the airway management team. additional airway equipment may be stored outside the negative pressure room as necessary. 4 all essential medications should be present before the procedure. rapid sequence induction (rsi) medications should be drawn up and labeled. depending on the patient"s hemodynamic status, push dose vasopressors or a norepinephrine infusion should be j o u r n a l p r e -p r o o f readily available. 56 ensure appropriate post-intubation analgesia, sedation, and paralyzing medications are present. 56 staff members who are not involved in the procedure should not be present during any aerosolgenerating procedure, including intubation. 4 there should be a clear delineation of roles and responsibilities on the team. three personnel are likely sufficient within the room: an airway operator, an airway assistant, and a healthcare provider to give the medications and monitor the patient (figure 3 ). 23 one to two team members should wait outside the room in ppe ready to enter if the primary team requires help or extra equipment, with an additional team member watching from the outside, ready to summon help rapidly if needed. 23 a designated safety/logistics officer should remain outside the room to observe for strict adherence to team safety and proper donning and doffing of ppe. a single team member may perform more than one role, depending on how many personnel are available. (4) team member to fetch additional equipment or call for help during the procedure, and to observe strict adherence to team safety and donning and doffing of ppe in the peri-procedure period (safety and logistics officer). a single team member may perform more than one role, depending on how many personnel are available. the choice of airway operator encompasses consideration of the available clinicians" airway expertise, predicted difficulty of intubation, patient factors, and clinician risk factors for poor outcomes if infected with sars-cov-2. 23, 56 while little guidance exists to risk stratify hcws who are exposed to potential aerosol-generating procedures, it is prudent to exclude staff who are over the age of 60 years; pregnant; immunosuppressed; and those with cardiac disease, respiratory diseases, and recent cancer. 5, 8, 23 j o u r n a l p r e -p r o o f the airway strategy, including preoxygenation strategy, primary plan, rescue plans, and transitions, should be standardized. the basic algorithm for intubation is similar to the difficult airway society (das) 2018 guideline for tracheal intubation of the critically ill patient (figure 4a and 4b) or the vortex approach (figure 4c) . 23, 67 there is emphasis on appropriate equipment selection, with a focus on closed systems to prevent viral transmission. 4, 23 closed suction systems should be used to minimize aerosolization. apneic oxygenation should be avoided in these patients. however, preoxygenation may be accomplished with a bag valve mask (bvm) and viral exhalation filter. 56, 68 the airway operator should ensure a tight bvm seal with two hands using the "v" grip while applying 10-15 cm of peep ( figure 5 ). this bvm is held passively in order to maintain peep, prevent decruitment and hypoxia. 56, 62 to improve mask seal and decrease airway operator fatigue, a niv mask may be used in conjunction with a bvm to preoxygenate the patient ( figure 6 ). for patients requiring manual ventilation, small tidal volumes are recommended. 68 elevation of the head of the bed and ramping may be utilized. 23 the preferred airway management technique is rsi with the use of a video laryngoscope (vl) by the most appropriate clinician to maximize first pass success. 18, 23, 53 in a systemic review and meta-j o u r n a l p r e -p r o o f analysis of 64 studies, vl reduced the risk of failed intubation with no impact on the rate of first pass success, hypoxia, or time to endotracheal intubation. 69 if possible, the vl setup should include a monitor screen separate from the handle to reduce potential exposure to the patient"s upper airway secretions. when available, a standard geometry video laryngoscope should be used in conjunction with a tracheal tube introducer (i.e., bougie), as this has been shown to improve first pass success when compared to a traditional stylet. 56, 70 awake flexible endoscopic intubation should be avoided, as the atomized local anesthesia may induce coughing. 68 when possible, direct laryngoscopy (dl) should be avoided as it places the face of the intubating clinician close to the patient"s airway and may increase the risk of exposure. 4, 18 rsi is recommended, as inadequate sedation or paralysis can produce coughing during laryngoscopy, generating aerosols. 4,56 a higher dose of sedative, as well as high-dose neuromuscular blockade should be administered during induction. 23, 56 nondepolarizing muscle relaxants such as rocuronium provide an advantage over depolarizing agents due to their extended duration of action, which prevents coughing should attempts at airway management be prolonged. 20 in order to improve ventilator synchrony and decrease aerosolization from inadequate sedation, prepare the patient"s post-intubation analgesia and sedation before the procedure. 56 if the initial intubation is unsuccessful and the patient requires oxygenation, a second-generation supraglottic airway device can be used to reduce aerosolization risk. 22, 56, 71 there is no robust evidence to suggest that supraglottic devices are more effective than bvm in this scenario. however, they are easy to place and have better seal pressure compared to bvm, thus reducing staff exposure. 20 if oxygenation cannot be maintained using a bvm or a supraglottic device, a cricothyroidotomy should be performed. 56 the simplified das 2018 guidance should be followed ( figure 4b) . we recommend the scalpel-bougie-tube technique in order to decrease potential j o u r n a l p r e -p r o o f aerosolization. 20, 56 while attempting an emergency front of neck access (fona) procedure, application of oxygenation from above is not recommended, as this may cause aerosolization when the cricothyroid membrane is punctured. 20 suction during the procedure should consist of a closed system with a viral filter. 72 after successful intubation, it is important to avoid ventilation until an appropriate viral filter is in place and the endotracheal tube cuff is inflated. 23 ensure tight connections between all parts of the ventilator circuit, and avoid unnecessary disconnections whenever possible. however, if the circuit must be disconnected, clamp the endotracheal tube to prevent aerosolization. endotracheal tube placement must be confirmed with waveform capnography, as ppe may preclude reliable auscultation of breath sounds. 4, 73 providers may also observe bilateral chest rise during assisted breaths, or alternatively, the ventilator waveform. 62 ultrasonography is a useful adjunct for confirming endotracheal intubation, as it can allow direct confirmation without the requirement for ventilations. 74 and a negative likelihood ratio of 0.01 (95% ci 0.01 to 0.02). 75 to prevent repeated exposures, a nasogastric tube may be inserted in the immediate post-intubation period. 23 clinicians may also consider obtaining deep tracheal sputum samples. ensure proper analgesia and sedation in order to prevent patient coughing and potential transmission of sars-cov-2. 56 any immediate post-intubation complications should be aggressively investigated and corrected. in a series of 202 covid-19 patients undergoing tracheal intubation in two hospitals in wuhan, china, peri-intubation hypotension (arterial blood pressure less than 90/60 mm hg) occurred in j o u r n a l p r e -p r o o f 22.3% of patients. 53 pneumothorax occurred in 5.9% of patients, while 2% suffered peri-intubation cardiac arrest. 53 peri-intubation hypotension should be managed with intravenous fluids and/or vasopressors, while pneumothorax may be corrected with chest tube drainage. after the immediate post-intubation period, equipment should be disposed of or decontaminated. individual ppe should be removed under the guidance of a trained observer. patients with covid-19 may develop acute respiratory failure and require respiratory support, as well as advanced airway management. 4 airway management in these patients is a high-risk procedure for hcws due to aerosolization and viral transmission. 11 the principles of airway management are similar between cvoid-19 and non-cvoid-19 patients, but with an enhanced focus on hcw safety. 56 a pragmatic approach to respiratory support in this population centers on appropriate infectious precautions (isolation, negative pressure rooms, and ppe), titrated support with exogenous oxygen, hfnc, niv, and endotracheal intubation. world health organization clinical features of patients infected with 2019 novel coronavirus in wuhan clinical characteristics of coronavirus disease 2019 in china practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-ncov) patients characteristics of and important lessons from the coronavirus disease 2019 (covid-19) outbreak in china: summary of a report of 72314 cases from the chinese center for disease control and prevention baseline characteristics and outcomes of 1591 patients infected with sars-cov-2 admitted to icus of the lombardy region covid-19 in critically ill patients in the seattle region -case series expert recommendations for tracheal intubation in critically ill patients with noval coronavirus disease clinical course and outcomes of critically ill patients with sars-cov-2 pneumonia in wuhan, china: a single-centered, retrospective, observational study. the lancet respiratory medicine clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china protecting health-care workers from subclinical coronavirus infection aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review pathological findings of covid-19 associated with acute respiratory distress syndrome novel 2019 coronavirus sars-cov-2 (covid-19): an updated overview for emergency clinicians clinical management of severe acute respiratory infection when novel coronavirus (ncov) infection is suspected the australian and new zealand intensive care society. covid-19 guidelines anzics covid-19 practice management guide: clinical management of covid-19 surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (covid-19) respiratory support for adult patients with covid-19 consensus statement: safe airway society principles of airway management and tracheal intubation specific to the covid-19 adult patient group why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? clinical infectious diseases staff safety during emergency airway management for covid-19 in hong kong consensus guidelines for managing the airway in patients with covid-19 high flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis high-flow nasal therapy in adults with severe acute respiratory infection: a cohort study in patients with 2009 influenza a/h1n1v high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure the experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of chongqing patient self-proning with high-flow nasal cannula improves oxygenation in covid-19 pneumonia comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial nasal high-flow therapy and dispersion of nasal aerosols in an experimental setting assessment of the potential for pathogen dispersal during high-flow nasal therapy risk factors for sars transmission from patients requiring intubation: a multicentre investigation in toronto exhaled air dispersion during high-flow nasal cannula therapy versus cpap via different masks exhaled air dispersion during coughing with and without wearing a surgical or n95 mask optimum insufflation capacity and peak cough flow in neuromuscular disorders severe sars-cov-2 infections: practical considerations and management strategy for intensivists beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study high-flow nasal cannula: mechanisms of action and adult and pediatric indications critically ill patients with 2009 influenza a(h1n1) infection in canada risk factors for noninvasive ventilation failure in critically ill subjects with confirmed influenza infection noninvasive ventilation in critically ill patients with the middle east respiratory syndrome. influenza other respir viruses ventilator-induced lung injury noninvasive ventilation for patients with hypoxemic acute respiratory failure effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome role of air distribution in sars transmission during the largest nosocomial outbreak in hong kong exhaled air dispersion during noninvasive ventilation via helmets and a total facemask minimise nosocomial spread of 2019-ncov when treating acute respiratory failure. the lancet effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial efficacy and safety of early prone positioning combined with hfnc or niv in moderate to severe ards: a multi-center prospective cohort study prone position for acute respiratory distress syndrome. a systematic review and meta-analysis critical care crisis and some recommendations during the covid-19 epidemic in china basing respiratory management of coronavirus on physiological principles emergency tracheal intubation in 202 patients with covid-19 in wuhan, china: lessons learnt and international expert recommendations intubation and ventilation amid the covid-19 outbreak an index combining respiratory rate and oxygenation to predict outcome of nasal high-flow therapy just the facts: airway management during the covid-19 pandemic detection of sars-cov-2 in different types of clinical specimens using simulation for training and to change protocol during the outbreak of severe acute respiratory syndrome airway challenges in critical care guidelines for the management of tracheal intubation in critically ill adults airway management in disaster response: a manikin study comparing direct and video laryngoscopy for endotracheal intubation by prehospital providers in level c personal protective equipment precautions for intubating patients with covid-19 barrier enclosure during endotracheal intubation the aerosol box for intubation in covid-19 patients: an in-situ simulation crossover study use of personal protective equipment during infectious disease outbreak and nonoutbreak conditions: a survey of emergency medical technicians the use of personal protective equipment for control of influenza among critical care clinicians: a survey study the vortex approach outbreak of a new coronavirus: what anaesthetists should know videolaryngoscopy versus direct laryngoscopy for adult patients requiring tracheal intubation effect of use of a bougie vs endotracheal tube and stylet on first-attempt intubation success among patients with difficult airways undergoing emergency intubation: a randomized clinical trial the laryngeal mask airway proseal(tm) as a temporary ventilatory device in grossly and morbidly obese patients before laryngoscope-guided tracheal intubation surgical considerations for tracheostomy during the covid-19 pandemic auscultation without contamination: a solution for stethoscope use with personal protective equipment ultrasound for airway management: an evidence-based review for the emergency clinician ultrasonography for the confirmation of endotracheal tube intubation: a systematic review and meta-analysis bl, tm, mr, mg, and dh conceived the idea for this manuscript and contributed substantially to the writing and editing of the review. this manuscript did not utilize any grants, and it has not been presented in abstract form. this clinical review has not been published, it is not under consideration for publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities key: cord-256688-yy7abob9 authors: chavez, summer; long, brit; koyfman, alex; liang, stephen y. title: coronavirus disease (covid-19): a primer for emergency physicians date: 2020-03-24 journal: am j emerg med doi: 10.1016/j.ajem.2020.03.036 sha: doc_id: 256688 cord_uid: yy7abob9 introduction: rapid worldwide spread of coronavirus disease 2019 (covid-19) has resulted in a global pandemic. objective: this review article provides emergency physicians with an overview of the most current understanding of covid-19 and recommendations on the evaluation and management of patients with suspected covid-19. discussion: severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the virus responsible for causing covid-19, is primarily transmitted from person-to-person through close contact (approximately 6 ft) by respiratory droplets. symptoms of covid-19 are similar to other viral upper respiratory illnesses. three major trajectories include mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ards). emergency physicians should focus on identifying patients at risk, isolating suspected patients, and informing hospital infection prevention and public health authorities. patients with suspected covid-19 should be asked to wear a facemask. respiratory etiquette, hand washing, and personal protective equipment are recommended for all healthcare personnel caring for suspected cases. disposition depends on patient symptoms, hemodynamic status, and patient ability to self-quarantine. conclusion: this narrative review provides clinicians with an updated approach to the evaluation and management of patients presenting to the emergency department with suspected covid-19. on january 30, 2020, the world health organization (who) designated an outbreak of a novel coronavirus not seen before in humans to be a "public health emergency of international concern" (pheic); this was followed by the declaration of a pandemic on march 11, 2020 [1, 2] . severe acute respiratory syndrome coronavirus 2 (sars-cov-2), previously referred to as 2019-ncov, is the virus responsible for causing coronavirus disease 2019 (covid-19) [3] [4] [5] [6] [7] . the pandemic traces its early beginnings to the report of a cluster of 27 unexplained pneumonia cases in late december 2019 originating from a seafood and live animal market in wuhan, hubei province, china [8] [9] [10] [11] . from the outset, the causative agent was thought to be viral, with most patients reporting fever or dyspnea [9, 11] . with unprecedented numbers of individuals under travel restrictions or quarantine, worldwide spread, and no known cure or vaccine yet available, covid-19 has proven a formidable adversary [12, [13] [14] [15] . the ebola virus disease (evd) outbreak of 2014 in west africa provided valuable lessons with regards to emergency preparedness, personal protective equipment use, and triage processes and underscored the important role that emergency physicians play on the frontlines of emerging infectious diseases [16] [17] [18] . we describe the virology, epidemiology, clinical presentation, radiographic and laboratory findings, current testing protocols, and management of patients presenting with covid-19 to the emergency department (ed). in this review article, we provide emergency physicians with best practices based on the rapidly evolving body of literature surrounding covid-19. sars-cov-2 is a member of the coronavirus family, named for the crown-like appearance of spikes on the virus surface [5, 19] . other members of the coronavirus family include middle east respiratory syndrome coronavirus (mers-cov) and sars-cov-1, as well as coronaviruses responsible for the common cold (figs. 1 and 2) [5, 6, 8, 19] . like mers-cov and sars-cov-1, sars-cov-2 is a betacoronavirus and is likely associated with an animal reservoir (e.g., bats) [6, 8, 14] . while an exact animal source has not been confirmed for covid-19, many of the early cases in china were linked to a live animal and seafood market [6, 14, 20, 21] . american journal of emergency medicine xxx (xxxx) xxx the majority of initial covid-19 cases were associated with travel to hubei province, china; however, a growing number of cases due to person-to-person transmission have been reported both in and outside of china (fig. 3) [8, 14, 22, 23] . up to 94% of covid-19 cases were reported to originate from hubei province in december 2019; as of march 2020, the greatest number of new cases are now being reported in italy, spain, germany, and the united states (u.s.) (figs. 3 and 4) [24] [25] [26] . based on what is known about other coronaviruses, experts believe covid-19 primarily spreads from person-to-person through close contact (approximately 6 ft) by respiratory droplets [4, 8, 14, 23, 27] . transmission of the virus through contaminated surfaces or fomites with subsequent contact with the eyes, nose, or mouth may also occur [14, 23, 27] . patients are felt to be at highest risk of spreading the illness when they are most symptomatic [23, 27] . limited data support viral shedding in asymptomatic patients while increased levels of viral shedding may be more pronounced in those critically ill [28] [29] [30] . current epidemiologic patterns of covid-19 in china indicate that it is highly contagious with sustained spread; the extent of person-to-person transmission within the u.s. was initially limited but has progressed now to community transmission in many parts of the country [23] . the current r 0 or basic reproduction number is estimated to be n2.2; for every case of covid-19 identified in the population, n2 additional cases are possible in the absence of adequate isolation. [20, [31] [32] [33] in an early epidemiologic analysis of 425 covid-19 cases in wuhan, china, the median patient age was 59 years, and 56% were male [20] . in the largest study to date of covid-19, comprising over 72,000 patient records (up to february 11, 2020) from china, 86.6% of patients were 30-79 years of age [34] . while 80.9% of these cases were reported to be mild, the overall case fatality rate was 2.3% [34] . few pediatric cases of covid-19 have been reported, with patients aged 0-19 years representing just 2.1% of all cases [34, 35] . approximately 3.8% of laboratory confirmed cases of covid-19 occurred in healthcare personnel, and 14.6% of these cases were either severe or critical [34] . to be classified as severe, the following characteristics were required: pao2/fio2 b 300, oxygen saturation ≤ 93%, presence of n50% lung infiltrates within 24-48 h, respirations ≥30 breaths/min, or dyspnea [34] . critical patients, defined as those with septic shock, multiple organ dysfunction/failure, and/or respiratory failure, accounted for approximately 5% of the study population with a case fatality rate of 49.0% [34, 24] . the highest case fatality rate was observed in those older than 80 years (14.8%) [34] . patients without comorbidities had a case fatality rate of just 0.9%, in contrast to those with comorbid conditions such as cardiovascular disease (10.5%) [34] . caution should be exercised in interpreting early findings, as underreporting and variable testing practices have been a concern with covid-19 [36, 37] . case fatality rates in hubei province have been reported to be 18% (95% confidence interval [ci] [11] [12] [13] [14] [15] [16] [17] [18] , while those outside mainland china range from 1.2-5.1% [38] . mortality rates have been calculated to be as high as 11-15% [39, 40] . when compared to other recent epidemics such as sars (9.56) or evd (39.53), the average case fatality rate (4.2%) for covid-19 is much lower (table 1) [41, 42] . in comparison, the 2009 h1n1 influenza pandemic and 2017 influenza season were responsible for approximately 220 times more cases [41, 42] . based on what is known about similar coronaviruses, the longest potential incubation period for covid-19 is thought to be 14 days from initial exposure [4, 6] . the mean incubation period is 5.2 days (95% ci 4.1-7.0) but can range from 2 to 14 days [4, 20, 43] . co-infections occur in 22-33% of patients and may be higher in critical patients [44, 45] . risk factors for severe covid-19 disease include advanced age, chronic medical conditions, immunocompromise, and cancer [46] . data regarding pregnancy and covid-19 are limited [47] . pregnant women and fetuses may be more vulnerable to covid-19 infection compared to the general population [48] . there are case reports of pregnant women diagnosed with covid-19 complicated by adverse outcomes including preterm birth [47] . historically, infants born to mothers with other coronaviruses such as mers-cov or sars-cov-1 have been small for gestational age or preterm [47] . newborn infants are also an at-risk population [48] . occupational exposure to pathogens is an inherent risk of working in healthcare settings [49] . during the 2003 sars outbreak, 9% of healthcare professionals (hcps) in toronto, canada participating in endotracheal intubation of infected patients became infected themselves [50] . in another study, 77% of sars patients in toronto had ties to the hospital setting, and 51% of cases were hcps [51] . during the h1n1 influenza pandemic, hcps were significantly more likely to develop infection (odds ratio [or] 2.08, 95% ci 1.73-2.51) with a pooled prevalence of 6.3% [52] . as covid-19 has disproportionately affected hcps, emergency physicians must be vigilant about potential exposure risks and adhere to appropriate infection prevention precautions [53, 54] . in italy, anywhere from 8 to 30% of hcps have been infected with sars-cov-2 [55, 56] . the symptoms of covid-19 are similar to other viral upper respiratory illnesses and include fever, cough, fatigue, and dyspnea [6, 8, 43] . the differential diagnosis for covid-19 should be tailored to the patient and their presenting symptoms and comorbidities. influenza, respiratory syncytial virus (rsv), other viral illnesses, and bacterial pneumonia should be considered, as well as other pulmonary diseases (ie, pulmonary embolism). completing a thorough yet focused history and physical examination and obtaining collateral history from family members are vital. aside from pulmonary symptoms, patients with covid-19 may initially present with more vague complaints including diarrhea, lethargy, myalgias, and nausea [40, 57] . patients may also experience headache, confusion, vomiting, pleurisy, sore throat, sneezing, rhinorrhea, and nasal congestion [40, 58] . a case series of 41 patients (median age 49.0 years) with covid-19 from wuhan, china found the most commonly reported symptoms were cough (76%), fever (98%), or dyspnea (55%) [39] . in the same case series, patients also reported myalgias/fatigue (44%), productive cough (28%), headache (8%), hemoptysis (5%), and diarrhea (3%) [39] . in a nationwide study of covid-19 cases from across china, the most common presenting symptoms included cough (68%), fever (44%), fatigue (38%), sputum production (34%), and shortness of breath (19%) [59] . fever was not a predominant symptom at the time of initial presentation. in patients with more severe disease, dyspnea may be present in 37% of patients and progress to acute lung injury in 15% of patients [60] . one study of 204 patients with confirmed covid-19 suggests 48.5% of patients have gastrointestinal (gi) symptoms [61] . these symptoms may include anorexia (83.8%), diarrhea (29.3%), vomiting (0.8%), and abdominal pain (0.4%). seven of the 204 patients had only gi symptoms with no respiratory symptoms [61] . atypical presentations of infection in general may be more likely in the elderly and immunocompromised, who may not mount a febrile response [62, 63] . to increase sensitivity and identify potential covid-19 patients sooner, the u.s. centers for disease control and prevention (cdc) recommends using a temperature cutoff of 100.0 f o [64] . patients older than 60 years of age and those with comorbidities may also present with more severe disease compared to other populations [58] . three major trajectories for covid-19 have been described: mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ards) necessitating aggressive resuscitative measures [65] . anywhere from 17 to 29% of patients may develop ards [39, 40] . other complications of covid-19 include secondary bacterial infection, acute kidney injury, septic shock, ventilator-associated pneumonia, and cardiac injury [39, 40] . an emergency medicine approach to covid-19 should focus on identifying and isolating patients at risk for infection, informing hospital infection prevention and local public health authorities, and engaging infectious disease and other specialists early in care. the world health organization (who) has established case and contact definitions for covid-19 to standardize global surveillance ( table 2 ). most patients with confirmed covid-19 have had a subjective or confirmed fever and/or symptoms of acute respiratory illness (e.g., cough, difficulty breathing) [66] . in concert with clinician judgment regarding patient presentations compatible with covid-19, cdc guidelines prioritize patients from defined populations for further evaluation and testing as persons under investigation (pui) ( table 3 ). these criteria are not exhaustive, and patients with an unestablished etiology or equivocal history of exposure may be considered for further testing on an individual basis [67] . confirmed local covid-19 cases in the setting of known community transmission should reduce the threshold for further covid-19 evaluation in the ed. collaboration with local and state public health departments is strongly recommended [62, 67] . a pui should be asked to wear a facemask to reduce risk of transmission to others in the immediate vicinity. fig. 5 details cdc recommendations for identifying and assessing suspected covid-19. emergency medical services (ems) directors and public health authorities working in conjunction with the cdc will need to modify emergency preparedness strategies to address covid-19 [68] . emergency medical dispatchers should consider whether callers describing risk factors and symptoms concerning for covid-19 should be a contact is a person who experienced any one of the following exposures during the 2 days before and the 14 days after the onset of symptoms of a probable or confirmed case: • face-to-face contact with a probable or confirmed case within 1 m and for n15 min; • direct physical contact with a probable or confirmed case; • direct care for a patient with probable or confirmed covid-19 disease without using proper personal protective equipment; or • other situations as indicated by local risk assessments. note: for confirmed asymptomatic cases, the period of contact is measured as the 2 days before through the 14 days after the date on which the sample was taken which led to confirmation. identified as a potential pui [30, 68] . if so, ems personnel arriving onscene as well as hcps at the receiving hospital should be notified immediately to ensure proper personal protective equipment (ppe) use and confirm that appropriate isolation facilities are available [30, 68] . once contact is made with the patient, initial triage and assessment should be done at least 6 ft or 2 meters away and minimized until the pui dons a facemask [68] . in addition to limiting the number of ems personnel in the patient compartment, those providing any direct patient care should follow standard, droplet (surgical mask), and contact precautions (gown and gloves) while wearing eye protection (face shield or goggles) [68] . airborne precautions (n95 respirator) should be employed if the patient is critically ill and/or if an aerosol-generating procedure is anticipated during transport. ideally, transport vehicles with isolated compartments or high efficiency particulate air (hepa) filtration should be used, and the patient should be transferred directly to a treatment room on arrival at the receiving healthcare facility [68] . after the patient has been transported and ems documentation is being completed, patient compartment doors should be left open to allow proper ventilation [68] . when cleaning the vehicle, disposable gown, gloves, surgical mask, and face shield should be worn [68] . routine cleaning should be followed by application of a hospital-grade disinfectant, preferably one approved by the u.s. environmental protection agency (epa) for use against emerging viral pathogens including sars-cov-2 [68] . patients presenting with symptoms concerning for covid-19 to the ed should be separated from other patients by at least 6 ft or 2 m and asked to wear a facemask [62, 69] . ideally, stable covid-19 puis would be identified at time of check-in or triage and then placed in a private room with the door closed [30, 64] . critically ill patients and those requiring aerosol-generating procedures should be placed in an airborne infection isolation room (aiir), also known as a negative pressure isolation room, with hepa filtration of the recirculated air [30, 69] . once a pui is identified, the appropriate health department or agency and institutional personnel should be notified in an expeditious manner [62, 67] . movement into and out of the patient's treatment room should be limited to only essential hcps involved in patient care [69] . while in the room, the pui may remove their facemask [69] . however, it is reasonable to ask the patient to wear a facemask during interactions with hcps (e.g., performing a physical examination) in the room as tolerated to contain respiratory droplets generated from coughing. hcps should either use alcohol-based hand sanitizer or wash their hands with soap and water before and after contact with a covid-19 pui [62, 69] . they should be trained in the appropriate use of ppe per hospital guidelines, including techniques to safely doff equipment protecting mucous membranes [69] . when caring for a stable pui, hcps should adhere to droplet (surgical mask), contact (gown and gloves), and standard precautions with the addition of eye protection (face shield or goggles) [8, 57, 62, 64, 69] . if a pui is critically ill or an aerosol-generating procedure (e.g., endotracheal intubation, suctioning of the airway, sputum induction) is necessary, hcps should escalate to airborne precautions with the use of a fitted n95 respirator in place of a surgical mask [62, 69, 70] . reusable respirators such as powered air purifying respirators (paprs) may also be used, but should be disinfected and maintained appropriately [69] . patients with a history of covid-19 exposure presenting with non-infectious symptoms may be evaluated and treated in adherence to standard precautions alone [64] . if portable studies (e.g., plain radiography) cannot be completed within the patient's room or the patient requires transport elsewhere within the ed or hospital by wheelchair or stretcher, hcps should don appropriate ppe [64, 70] . healthcare professionals at the destination or receiving location should be made aware of the patient's arrival and likewise don appropriate ppe [64, 71] . patients leaving their treatment room should wear a facemask, be dressed in a clean hospital gown (when possible), perform hand hygiene, and be educated in proper respiratory hygiene [71] . personnel cleaning empty pui rooms should follow droplet, contact, and standard precautions with eye protection as infectious particles may be present [63] . it is unclear how long sars-cov-2 remains in the air, but drawing parallels from other airborne disease such as tuberculosis can be helpful, particularly if an aerosol-generating procedure has been performed [63] . frequently used surfaces should be cleaned at least twice daily with implementation of standard institutional cleaning procedures [71] . intubation is a high-risk procedure due to the aerosolization of respiratory droplets [30, 72] . rescue intubations should be avoided whenever possible as complete adherence to ppe may be inadequate in a timesensitive critical scenario [72] . society of critical care medicine (sccm) surviving sepsis covid-19 guidelines recommend performing endotracheal intubation under airborne precautions, including use of a fitted n95 respirator and placement of the patient in an aiir [70] . based on prior cases of hcps infected with sars-cov-1 while using n95 respirators, some experts recommend using a papr [72] . the most experienced provider should intubate [70, 72] . to reduce inadvertent contamination by touching one's face or hair, a full face shield and head cover is recommended if a papr is not used [30, 72] . wrist exposure can be minimized by using longer-sleeved gloves or vertically taping gloves to the gown [30] . applying tape circumferentially makes removing ppe more difficult and does not have added benefit [30] . shoe covers should be avoided, as they can lead to accidental selfcontamination. instead, impermeable shoes that can be appropriately decontaminated should be worn [30] . if available, coveralls with or without a hood may be used, but processes and training in safe doffing should be established beforehand as hcps may be less experienced in using these ppe ensembles [30] . in order to inform decisions related to infection control. 2. other symptomatic individuals such as, older adults and individuals with chronic medical conditions and/or an immunocompromised state that may put them at higher risk for poor outcomes (e.g., diabetes, heart disease, receiving immunosuppressive medications, chronic lung disease, chronic kidney disease). 3. any persons including healthcare personnel a , who within 14 days of symptom onset had close contact b with a suspect or laboratory-confirmed c covid-19 patient, or who have a history of travel from affected geographic areas d within 14 days of their symptom onset. notes: a for healthcare personnel, testing may be considered if there has been exposure to a person with suspected covid-19 without laboratory confirmation. because of their often extensive and close contact with vulnerable patients in healthcare settings, even mild signs and symptoms (e.g., sore throat) of covid-19 should be evaluated among potentially exposed healthcare personnel. hcps may consider double gloving and positioning waste and other transport receptacles close by to limit droplet and/or contact transmission when securing contaminated equipment for disposal or reprocessing [72] . preoxygenation should be optimized with nonaerosol generating strategies including head of bed elevation, jaw thrust, and use of positive end expiratory pressure valves. fiberoptic laryngoscopy should be avoided unless absolutely necessary as atomization of anesthetic will cause the virus to become aerosolized [72] . preoxygenation for at least 5 min with 100% oxygen before performing rapid sequence intubation (rsi) may be used with nasal cannula, though this may increase the risk of contamination [30, 72] . to reduce this risk, a surgical mask can be placed on the patient over the device. non-invasive positive pressure ventilation (nippv) may increase risk of aerosolization and is not recommended for preoxygenation [30, 72] . a high efficiency hydrophobic filter should be used between the facemask and the rest of the respiratory circuit [72] . video laryngoscopy is preferred to direct laryngoscopy to increase distance between the intubator and the patient [30, 70] . a closed system should be utilized for suctioning. once the intubation is complete, the emergency physician should immediately place the laryngoscope in their outer glove along with all other equipment used for intubation in a double ziplocked plastic bag [72] . the presence of a high-efficiency particulate air (hepa) filter should be verified in the expiratory limb of the mechanical ventilator prior to patient use. the cdc has developed a real time reverse transcription polymerase chain reaction (rt-pcr) assay for detecting sars-cov-2 in upper and lower respiratory specimens obtained from covid-19 puis [73] . [74] a nasopharyngeal swab specimen should be collected for testing [75] . for lower respiratory tract specimens, sputum can be obtained from patients with productive cough, otherwise bronchoalveolar lavage or tracheal aspirate can be substituted [75] . serum samples are not necessary [75, 76] . there are few data available regarding sensitivity and specificity for the test, but false negatives may be seen in asymptomatic individuals or those early in the course of their disease who may not have high viral burden [27] . patients who test negative for covid-19 using a sample taken while they were symptomatic likely do not have the disease [6] . however, the sensitivity of rt-pcr has been reported to range from 66% to 80% [77] . a single negative rt-pcr should not be used to exclude the diagnosis, especially if the patient is in the early stages of the disease with no severe symptoms. a patient with negative rt-pcr with continued suspicion of covid-19 should be isolated and rechecked several days later. molecular testing (e.g., respiratory virus panel) for alternative diagnoses such as influenza should be considered for all puis [67] . however, co-infection with other viruses may occur. anemia, lymphopenia, hypoxemia, abnormal kidney and liver function, elevated creatine kinase and d-dimer, thrombocytopenia, and increased lactate dehydrogenase can be present [39, 40, 58] . lymphocytopenia can occur in up to 80% of patients [60] . interestingly, one study found procalcitonin was elevated in just 6% of patients, while other inflammatory markers like serum ferritin and c-reactive protein were elevated [40] . troponin and brain natriuretic peptide may be elevated in those with cardiac involvement and should be obtained in patients with suspected myocardial infarction or heart failure [78] . advanced imaging such as computed tomography (ct) is not required for diagnosis and may create additional infection prevention challenges in the ed. however, if obtained, ct may demonstrate several findings. lung findings may be present on imaging before patients develop clinical manifestations. in a case series of patients from wuhan, china admitted with covid-19, 100% had chest ct findings consistent with pneumonia [39] . patients may also have radiographic groundglass opacities [58] . another study of 99 covid-19 patients found 75% of patients had bilateral pneumonia, 25% had unilateral pneumonia, and 14% had mottling and ground-glass opacities on chest x-ray and ct imaging [40] . ultrasound can be utilized as well, as it is repeatable and reliable, has no radiation, and is inexpensive. ultrasound findings depend on the stage and severity of the disease, and it cannot detect lesions deeper in the lung. patients with covid-19 typically demonstrate an irregular/thickened pleural line, scattered/confluent b lines, consolidations of various sizes, and both non-translobar and translobar consolidations on lung ultrasound [79] . pleural effusions are typically small and localized if they are present, and abnormalities are typically found in multiple lung zones. currently, no specific treatments exist nor are recommended for patients with covid-19 [4, 15, 62] . several vaccines are under study, including dna-based, vector-based, and protein based vaccines [80] . supportive care is the mainstay of treatment, preferably with acetaminophen [4, 15] . if pneumonia is present on imaging or the patient is critically ill, antibiotics are recommended. patients presenting with respiratory insufficiency in the setting of potential covid-19 infection should be given supplementary oxygen to maintain an oxygenation saturation ≥90% but no higher than 96% [62, 70] . up to 76% of patients require oxygen therapy [40] . for those with acute hypoxemic respiratory failure who require intubation, endotracheal intubation should be performed. for those with hypoxemic respiratory failure who do not require intubation but who do not improve with conventional oxygen therapies, high flow nasal cannula (hfnc) is recommended over noninvasive positive pressure ventilation (nippv) [70] . if hfnc is not available and there is no urgent need for intubation, a trial of nippv ventilation is recommended with frequent reassessment, though nippv increases the risk of aerosolization [70] . nippv may result in patient improvement. the sccm does not make a clear recommendation for helmet nippv compared to mask nippv [70] . while most recommend avoiding nippv due to the risk of aerosolization, it can be utilized safely if high risk patients are cohorted and clinicians use appropriate ppe [81] . patients who decline despite use of hfnc or nippv should be intubated [70] . if intubation is indicated, airborne precautions should be used with the patient ventilated using tidal volumes of 4-8 ml/kg of predicted body weight and plateau pressures b30 cm h 2 o [62] . if available, patients with severe ards may benefit from prone ventilation n12 h per day [62, 70] . over-resuscitation with intravenous fluids should be avoided, which can potentially worsen oxygenation [62] . even when covid-19 is suspected as the cause of the patient's symptoms, the who recommends administering empiric antibiotics and a neuraminidase inhibitor within 1 h of identifying sepsis [62] . early recognition of septic shock is critical, with management of sepsis focusing on intravenous fluid resuscitation and antibiotics [62] . a conservative resuscitation strategy with buffered/balanced crystalloids is recommended for those in shock, and hypotonic crystalloids should be avoided [62, 70] . vasopressors, preferentially norepinephrine, are indicated for persistent shock with a goal map of 60-65 mmhg [62, 70] . for those with continued shock despite norepinephrine, vasopressin should be added, rather than increasing norepinephrine dose [70] . if cardiac dysfunction is present and there is persistent hypoperfusion, dobutamine is recommended [70] . systemic steroids (hydrocortisone 200 mg per day) should be considered in those with vasopressor-refractory shock or for those with another indication for steroids such as chronic obstructive pulmonary disease exacerbation [22, 62, 70] . without delaying antibiotic administration, bacterial blood cultures should be obtained [62] . clinical trials of investigational drugs and antivirals are underway, although none are currently approved by the u.s. food and drug administration (fda) ( table 4 ) [4, 46] . remdesivir has demonstrated activity against mers-cov and sars-cov in vitro and animal models [82, 83] . an in vitro study found that remdesivir and chloroquine inhibit viral infection, but further study is required [84, 85] . results from a single study of over 100 covid-19 patients found chloroquine was superior to control in reducing pneumonia exacerbation, improving imaging findings and virus-negative conversion, and shortening the course of the disease [86] . a study evaluating lopinavir-ritonavir found no improvement in patient survival or differences in detectable viral rna [87] . hydroxychloroquine and azithromycin are also under study [88] . in a single prospective, observational study of 36 patients with covid-19, those receiving hydroxychloroquine demonstrated higher rates of viral load reduction/disappearance, though no patient centered outcomes were assessed [88] . other medications under study include tocilizumab and favipiravir [89, 90] . there are no clear data supporting harm or benefit with angiotensin converting enzyme inhibitors or ace receptor blockers (arbs) [91, 92] . unless authorized through a clinically approved trial or monitored emergency use of unregistered interventions framework (meuri), unlicensed treatments should not be administered [62] . continuous renal replacement therapy (crrt), extracorporeal membrane oxygenation (ecmo), and immunoglobulin have been utilized for management, but have not been definitively shown to be beneficial [40] . patients with severe symptoms, hypoxemia requiring oxygen supplementation, or high risk for clinical deterioration (i.e. pneumonia on radiograph, severe comorbidities) may require admission for further management and monitoring. patients with mild symptoms and no significant comorbidities without concern for deterioration of clinical condition may be candidates for discharge, self-quarantine for two weeks, and home monitoring [93] . these patients must have the ability to be safely isolated at home to prevent transmission to others and be carefully monitored [22] . social distancing is a vital component of reducing the spread of the virus, comprised of limiting events, mass gatherings, and even small group meeting [94] . individuals should remain 6 ft or 2 meters apart from other individuals. health departments should be involved early in the care of these patients and can assist with decisions regarding disposition, further surveillance, and testing, especially until confirmatory test results are available [57, 62] . emergency physicians should counsel these patients to return for worrisome symptoms including new or worsening pulmonary complaints and fever [57, 62] . development of a clinical pathway among emergency physicians, infectious disease specialists, and health departments is critical to safely evaluate covid-19 puis in the community. covid-19 is a novel coronavirus that has affected an unprecedented number of people to date. patients typically present with a combination of fever or cough and have a history of exposure to either a close contact with covid-19 or travel to an affected geographic area. while most patients will have mild disease, some may develop severe complications including ards and multi-organ failure, with some succumbing to the disease. special consideration should be given to those at the extremes of age, the immunocompromised, or pregnant women. no curative treatment is currently approved. emergency physicians should obtain a detailed travel history from all patients and suspect covid-19 in patients presenting with symptoms of an acute upper respiratory illness and fever. early recognition and isolation of a patient with covid-19 in the ed may help decrease exposure to other patients and healthcare personnel. future research is necessary to expand our collective knowledge of covid-19 and optimize patient outcomes. none. author contributions sc, sl, ak, and bl conceived the idea for this manuscript and contributed substantially to the writing and editing of the review. none. statement on the second meeting of the international health regulations (2005) emergency committee regarding the outbreak of novel coronavirus world health organization. who director-general's opening remarks at the media briefing on covid-19 -11 world health organization. who director-general's remarks at the media briefing on 2019-ncov on 11 q&a on coronaviruses new images of novel coronavirus sars-cov-2 now available|nih: national institute of allergy and infectious diseases ovel coronavirus (2019-ncov) frequently asked questions and answers naming the coronavirus disease (covid-2019) and the virus that causes it a timeline of the coronavirus. the new york times chp closely monitors cluster of pneumonia cases on mainland coronavirus travel restrictions, across the globe. the new york times 780 million people in china face travel restrictions over coronavirus outbreak novel coronavirus (2019-ncov) situation summary novel coronavirus (2019-ncov) prevention & treatment. centers for disease control and prevention the impact of a case of ebola virus disease on emergency department visits in metropolitan dallas-fort worth ebola virus disease: preparedness and infection control lessons learned from two biocontainment units inform: emergency department evaluation and management for patients under investigation (puis) for ebola virus disease (evd)|emergency services|clinicians|ebola (ebola virus disease early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia covid-19) covid-19). date novel coronavirus (2019-ncov) transmission. centers for disease control and prevention general's remarks at the media briefing on covid-2019 outbreak on 17 february world health organization novel coronavirus (2019-ncov) cases in the u.s. centers for disease control and prevention transcript for cdc media telebriefing sars-cov-2 viral load in upper eespiratory specimens of infected patients presumed asymptomatic carrier transmission of covid-19 practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-ncov) patients. can j anesth can anesth covid-19-new insights on a rapidly changing epidemic pattern of early human-to-human transmission of wuhan how does the new coronavirus compare with the flu? livescience the epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (covid-19) -china more outbreak details emerge as covid-19 cases top 70,000 facts vs. fears: five things to help weigh your coronavirus risk report 2: estimating the potential total number of novel coronavirus cases in wuhan city report 4: severity of 2019-novel coronavirus (ncov) clinical features of patients infected with 2019 novel coronavirus in wuhan epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the global burden of disease study novel coronavirus (2019-ncov) symptoms clinical diagnosis of 8274 samples with 2019-novel coronavirus in wuhan higher co-infection rates in covid19 novel coronavirus (2019-ncov) clinical care novel coronavirus (2019-ncov) pregnant women what are the risks of covid-19 infection in pregnant women? infectious agents -niosh workplace safety and health topic intubation of sars patients: infection and perspectives of healthcare workers clinical features and short-term outcomes of 144 patients with sars in the greater toronto area the occupational risk of influenza a (h1n1) infection among healthcare personnel during the 2009 pandemic: a systematic review and meta-analysis of observational studies american college of emergency physicians. two emergency physicians in critical condition 2 er doctors at rush oak park hospital test positive for coronavirus. nbc chic italy has a world-class health system. the coronavirus has pushed it to the breaking point doctors: covid-19 pushing italian icus toward collapse novel coronavirus (2019-ncov) flowchart for healthcare professionals a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster clinical characteristics of coronavirus disease 2019 in china clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china clinical characteristics of covid-19 patients with digestive symptoms in hubei, china: a descriptive, cross-sectional, multicenter study clinical management of severe acute respiratory infection when novel coronavirus (ncov) infection is suspected covid-19) interim infection prevention and control recommendations novel coronavirus (2019-ncov) healthcare infection prevention and control faqs for covid-19 covid-19: what is next for public health? covid-19): evaluating and testing persons for coronavirus disease 2019 (covid-19) novel coronavirus (2019-ncov) evaluating and reporting pui covid-19) interim guidance for emergency medical services (ems) systems and 911 public safety answering points (psaps) for covid-19 in the united states novel coronavirus (2019-ncov) infection control surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease infection prevention and control for coronavirus disease (covid-19): interim guidance for acute healthcare settings anesthesia patient safety foundation novel coronavirus (2019-ncov) testing novel coronavirus (2019-ncov) information for laboratories covid-19 requests for diagnostic panels and virus covid-19) interim guidelines for collecting, handling, and testing clinical specimens from persons under investigation (puis) for coronavirus disease 2019 (covid-19) detection of sars-cov-2 in different types of clinical specimens correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases. radiology troponin and bnp use in covid-19. latest in cardiology. http%3a%2f% 2fwww.acc.org%2flatest-in-cardiology%2farticles%2f2020%2f03%2f18%2f15%2f25% 2ftroponin-and-bnp-use-in-covid19 findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic. intensive care med world health organization. draft landscape of covid-19 candidate vaccines episode 38 -covid-19 update. an interview with andrea duca, md. ebmedicine the antiviral compound remdesivir potently inhibits rna-dependent rna polymerase from middle east respiratory syndrome coronavirus compounds with therapeutic potential against novel respiratory 2019 coronavirus remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-ncov) in vitro drug treatment options for the 2019-new coronavirus (2019-ncov) breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of covid-19 associated pneumonia in clinical studies a trial of lopinavir-ritonavir in adults hospitalized with severe covid-19 hydroxychloroquine and azithromycin as a treatment of covid-19: results of an open-label non-randomized clinical trial tocilizumab vs crrt in management of cytokine release syndrome (crs) in covid-19 (tacos) favipiravir combined with tocilizumab in the treatment of corona virus disease angiotensin-converting enzyme 2 (ace2) as a sars-cov-2 receptor: molecular mechanisms and potential therapeutic target are patients with hypertension and diabetes mellitus at increased risk for covid-19 infection? home care for patients with suspected novel coronavirus (ncov) infection presenting with mild symptoms and management of contacts covid-19): interim us guidance for risk assessment and public health management of persons with potential coronavirus disease 2019 (covid-19) exposures: geographic risk and contacts of laboratory-confirmed cases this manuscript did not utilize any grants, and it has not been presented in abstract form. this clinical review has not been published, it is not under consideration for publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in english or in any other language, including electronically without the written consent of the copyright-holder. this review does not reflect the views or opinions of the u.s. government, department of defense, u.s. army, u.s. air force, brooke army medical center, or saushec em residency program.